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Adamopoulou E, Dimitriadis K, Kyriakoulis K, Pyrpyris N, Beneki E, Fragkoulis C, Konstantinidis D, Aznaouridis K, Tsioufis K. Defining "Vulnerable" in coronary artery disease: predisposing factors and preventive measures. Cardiovasc Pathol 2025; 77:107736. [PMID: 40228760 DOI: 10.1016/j.carpath.2025.107736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 03/16/2025] [Accepted: 04/10/2025] [Indexed: 04/16/2025] Open
Abstract
The likelihood of a plaque to cause an acute coronary syndrome (ACS) depends on several factors, both lesion- and patient-related. One of the most investigated and established contributing factors is the presence of high-risk or "vulnerable plaque" characteristics, which have been correlated with increased incidence of major adverse cardiovascular events (MACE). The recognition, however, that a significant percentage of vulnerable plaques do not result in causing clinical events has led the scientific community towards the more multifaceted concept of "vulnerable patients". Incorporating the morphological features of an atherosclerotic plaque into its hemodynamic surroundings can better predict the chance of its disruption, as altered fluid dynamics play a significant role in plaque destabilization. The advances in coronary imaging and the field of computational fluid dynamics (CFD) can contribute to develop more accurate lesion- and patient-related ACS prediction models that take into account both the morphology of a plaque and the forces applied upon it. The aim of this review is to provide the latest data regarding the aforementioned predictive factors as well as relevant preventive measures.
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Affiliation(s)
- Eleni Adamopoulou
- First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27, Athens, Greece
| | - Kyriakos Dimitriadis
- First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27, Athens, Greece.
| | - Konstantinos Kyriakoulis
- First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27, Athens, Greece
| | - Nikolaos Pyrpyris
- First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27, Athens, Greece
| | - Eirini Beneki
- First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27, Athens, Greece
| | - Christos Fragkoulis
- First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27, Athens, Greece
| | - Dimitris Konstantinidis
- First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27, Athens, Greece
| | - Konstantinos Aznaouridis
- First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27, Athens, Greece
| | - Konstantinos Tsioufis
- First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27, Athens, Greece
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Seshadri H, Gunasekaran D, Mohammad A, Rachoori S, Rajakumar HK. Myocardial ischemia in nonobstructive coronary arteries: A review of diagnostic dilemmas, current perspectives, and emerging therapeutic innovations. World J Cardiol 2025; 17:106541. [DOI: 10.4330/wjc.v17.i5.106541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 03/27/2025] [Accepted: 05/07/2025] [Indexed: 05/23/2025] Open
Abstract
Myocardial infarction with nonobstructive coronary arteries is a unique presentation of acute coronary syndrome occurring in patients without significant coronary artery disease. Its pathophysiology involves atherosclerotic and nonatherosclerotic mechanisms such as plaque erosion, coronary microvascular dysfunction, vasospasm, spontaneous coronary artery dissection, autoimmune and inflammatory diseases, and myocardial oxygen supply-demand imbalance. A systematic approach to diagnosis is needed due to the diverse range of underlying causes. Cardiac troponins confirm the myocardial injury and coronary angiography rules out significant obstruction. Cardiac magnetic resonance imaging differentiates ischemic from nonischemic causes, and additional investigations, such as intravascular ultrasound, optical coherence tomography, and provocative testing, play a role in identifying the etiology to guide management strategies. Atherosclerotic cases require antiplatelet therapy and statins, vasospastic cases respond to calcium channel blockers, spontaneous coronary artery dissection is typically managed conservatively, and coronary microvascular dysfunction may require vasodilators. Lifestyle modifications and cardiac rehabilitation are essential for improving outcomes. The prognosis of patients experiencing recurrent events despite treatment is uncertain, but long-term outcomes depend on the etiology, highlighting the need for personalized management. Future research should focus on refining diagnostic protocols and identifying optimal therapeutic strategies. Randomized controlled trials are necessary to establish evidence-based treatments for different subtypes of myocardial infarction with nonobstructive coronary arteries.
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Affiliation(s)
- Hariharan Seshadri
- Institute of Internal Medicine, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai 600003, Tamil Nadu, India
| | - Dhaiyanitha Gunasekaran
- Department of General Surgery, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
| | | | - Srinivas Rachoori
- Department of General Surgery, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
| | - Hamrish Kumar Rajakumar
- Department of General Surgery, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
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Sekimoto T, Tatsuya S, Kawakami R, Sakamoto A, Tanaka T, Hamana T, Finn AV, Virmani R. Biomarkers Differentiating Plaque Erosion from Stable Plaque. Curr Atheroscler Rep 2025; 27:58. [PMID: 40411530 DOI: 10.1007/s11883-025-01303-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/07/2025] [Indexed: 05/26/2025]
Abstract
PURPOSE OF REVIEW Plaque erosion is the second most frequent cause of acute coronary syndrome, yet the biological processes and biomarkers associated with erosion remain incompletely understood. This review aims to examine the current understanding of plaque erosion, with a focus on identifying potential biomarkers. RECENT FINDINGS Recent studies have identified distinct pathophysiological characteristics associated with plaque erosion, including variations in inflammatory response and immune cell infiltration within the culprit lesions and thrombi. Additionally, differences in the expression patterns of specific molecules have been noted, suggesting unique underlying mechanisms that contribute to plaque erosion. Understanding the differential expression and role of immune cells and biomarkers in erosion may be crucial for developing targeted therapies. The identification of biomarkers may help in the early detection and treatment of erosion-prone plaques, potentially reducing the incidence of acute coronary events.
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Affiliation(s)
- Teruo Sekimoto
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, USA
| | - Shiraki Tatsuya
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, USA
| | - Rika Kawakami
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, USA
| | - Atsushi Sakamoto
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, USA
| | - Takamasa Tanaka
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, USA
| | - Tomoyo Hamana
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, USA
| | - Aloke V Finn
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, USA
- School of Medicine, University of Maryland, Baltimore, MD, USA
| | - Renu Virmani
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, USA.
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Mori H, Yamamoto MH, Mizukami T, Kobayashi N, Wakabayashi K, Kondo S, Sekimoto T, Sambe T, Yasuhara S, Sugiyama T, Kakuta T, Mitomo S, Nakamura S, Takano M, Yonetsu T, Dohi T, Yamashita J, Yamaguchi J, Kimura S, Higuma T, Natsumeda M, Ikari Y, Suwa S, Suzuki H, Shinke T, TACTICS investigators. Significant Stenosis Without Thrombus: Is It the Third Most Common Morphology of Acute Coronary Syndrome? CJC Open 2025; 7:641-648. [PMID: 40433211 PMCID: PMC12105524 DOI: 10.1016/j.cjco.2025.01.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 01/20/2025] [Indexed: 05/29/2025] Open
Abstract
Background Significant stenosis without thrombus (SSWT) is sometimes observed in patients with acute coronary syndrome (ACS). However, its incidence and clinical features remains unclear. Method This substudy of the TACTICS registry included patients with ACS (n = 702) undergoing emergency percutaneous coronary intervention using optical coherence tomography. Using this registry data, we compared the clinical features of SSWT in patients with ACS. Major adverse cardiac events were defined as cardiac death, nonfatal myocardial infarction, heart failure, or ischemia-driven revascularization at 1 year. Results Plaque rupture (PR; n = 411, 59.1%) and plaque erosion (PE; n = 178, 25.6%) were the 2 major morphologies, followed by SSWT (n = 64, 9.1%) and calcified nodule (CN; n = 28, 4.0%). Patients with SSWT were slightly older than those with PR and PE, but younger than those with CN. In the SSWT, non-ST elevation myocardial infarction was the main type of ACS, followed by unstable angina and ST-elevation myocardial infarction (63%, 22%, and 15%, respectively). Lesions were less complex with a lower proportion of type B2 or C, shorter procedure time, lower proportion of multivessel disease, and lower syntax score, which led to a lower incidence of major adverse cardiac events. Conclusion SSWT was the third most common morphology of ACS, with clinical features different from those of PR, PE, and CN.
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Affiliation(s)
- Hiroyoshi Mori
- Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Kanagawa, Japan
| | - Myong Hwa Yamamoto
- Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, Tokyo, Japan
| | - Takuya Mizukami
- Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, Tokyo, Japan
- Division of Clinical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan
| | - Nobuaki Kobayashi
- Department of Cardiology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Kohei Wakabayashi
- Division of Cardiology, Cardiovascular Center, Showa University Koto-Toyosu Hospital, Tokyo, Japan
| | - Seita Kondo
- Division of Cardiology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Teruo Sekimoto
- Division of Cardiology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Takehiko Sambe
- Division of Clinical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan
| | - Sakiko Yasuhara
- Division of Clinical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan
| | - Tomoyo Sugiyama
- Division of Cardiovascular Medicine, Tsuchiura Kyodo General Hospital, Ibaraki, Japan
| | - Tsunekazu Kakuta
- Division of Cardiovascular Medicine, Tsuchiura Kyodo General Hospital, Ibaraki, Japan
| | - Satoru Mitomo
- Department of Cardiovascular Medicine, New Tokyo Hospital, Chiba, Japan
| | - Sunao Nakamura
- Department of Cardiovascular Medicine, New Tokyo Hospital, Chiba, Japan
| | - Masamichi Takano
- Department of Cardiology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Taishi Yonetsu
- Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Tomotaka Dohi
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Jun Yamashita
- Department of Cardiology, Tokyo Medical University Hospital, Tokyo, Japan
| | - Junichi Yamaguchi
- Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan
| | - Shigeki Kimura
- Department of Cardiology, Yokohama Minami Kyosai Hospital, Kanagawa, Japan
| | - Takumi Higuma
- Division of Cardiology, Department of Internal Medicine, Kawasaki Municipal Tama Hospital, Kanagawa, Japan
| | - Makoto Natsumeda
- Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan
| | - Yuji Ikari
- Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan
| | - Satoru Suwa
- Department of Cardiovascular Medicine, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Hiroshi Suzuki
- Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Kanagawa, Japan
| | - Toshiro Shinke
- Division of Cardiology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan
| | - TACTICS investigators
- Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Kanagawa, Japan
- Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, Tokyo, Japan
- Division of Clinical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan
- Department of Cardiology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
- Division of Cardiology, Cardiovascular Center, Showa University Koto-Toyosu Hospital, Tokyo, Japan
- Division of Cardiology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan
- Division of Cardiovascular Medicine, Tsuchiura Kyodo General Hospital, Ibaraki, Japan
- Department of Cardiovascular Medicine, New Tokyo Hospital, Chiba, Japan
- Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Department of Cardiology, Tokyo Medical University Hospital, Tokyo, Japan
- Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan
- Department of Cardiology, Yokohama Minami Kyosai Hospital, Kanagawa, Japan
- Division of Cardiology, Department of Internal Medicine, Kawasaki Municipal Tama Hospital, Kanagawa, Japan
- Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan
- Department of Cardiovascular Medicine, Juntendo University Shizuoka Hospital, Shizuoka, Japan
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5
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Nakahara T, Fujimoto S, Jinzaki M. Molecular imaging of cardiovascular disease: Current status and future perspective. J Cardiol 2025; 85:386-398. [PMID: 39922562 DOI: 10.1016/j.jjcc.2025.01.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 01/15/2025] [Accepted: 01/28/2025] [Indexed: 02/10/2025]
Abstract
Advancements in knowledge of cardiovascular disease, pharmacology, and chemistry have led to the development of newer radiopharmaceuticals and targets for new and more suitable molecules. Molecular imaging encompasses multiple imaging techniques for identifying the characteristics of key components involved in disease. Despite its limitations in spatial resolution, the affinity for key molecules compensates for disadvantages in diagnosing diseases and elucidating their pathophysiology. This review introduce established molecular tracers involved in clinical practice and emerging tracers already applied in clinical studies, classifying the key component in A: artery, specifically those vulnerable plaque (A-I) inflammatory cells [18F-FDG]; A-II) lipid/fatty acid; A-III) hypoxia; A-IV) angiogenesis; A-V) protease [18F/68Ga-FAPI]; A-VI) thrombus/hemorrhage; A-VII) apoptosis and A-VIII) microcalcification [18F-NaF]) and B: myocardium, including myocardial ischemia, infarction and myocardiopathy (B-I) myocardial ischemia; B-II) myocardial infarction (myocardial damage and fibrosis); B-III) myocarditis and endocarditis; B-IV) sarcoidosis; B-V) amyloidosis; B-VI) metabolism; B-VII) innervation imaging). In addition to cardiovascular-specific tracers tested in animal models, many radiotracers may have been developed in other areas, such as oncology imaging or neuroimaging. While this review does not cover all available tracers, some of them hold potential for future use assessing cardiovascular disease. Advances in molecular biology, pharmaceuticals, and imaging sciences will facilitate the identification of precise disease mechanisms, enabling precise diagnoses, better assessment of disease status, and enhanced therapeutic evaluation in this multi-modality era.
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Affiliation(s)
- Takehiro Nakahara
- Department of Radiology, Keio University School of Medicine, Tokyo, Japan.
| | - Shinichiro Fujimoto
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Masahiro Jinzaki
- Department of Radiology, Keio University School of Medicine, Tokyo, Japan
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6
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Tang C, Shi G, Jia R, Pei X, Wang C, Du Z, Li S, Wan P, Sun S, Peng C, Li S, Sun P, Yu B, Dai J. Chronic Disturbed Flow Induces Superficial Erosion-Prone Lesion via Endothelial-to-Mesenchymal Transition in a DNA Methyltransferase-Dependent Manner. J Atheroscler Thromb 2025; 32:608-629. [PMID: 39551496 PMCID: PMC12055510 DOI: 10.5551/jat.64990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Accepted: 09/23/2024] [Indexed: 11/19/2024] Open
Abstract
AIM Superficial erosion accounts for approximately one-third of all cases of acute coronary syndrome (ACS). Previously, we found that a nearby bifurcation is independently associated with superficial erosion; however, the effect of long-term oscillatory flow on superficial erosion remains unexplored. Endothelial-to-mesenchymal transition (EndMT) is a dynamic process in which endothelial cells acquire mesenchymal properties and, in turn, give rise to smooth muscle cell (SMC)-like cells and extracellular matrix (ECM) accumulation, similar to the autopsy pathology of superficial erosion. This finding prompted us to suspect that EndMT plays a role in the effect of chronic oscillatory flow on superficial erosion. METHODS We established oscillatory flow in mouse carotid arteries and analyzed neointimal hyperplasia, endothelial continuity, ECM content, and EndMT markers 4 weeks later. Furthermore, bioinformatic data analyses and in vitro studies were performed to elucidate the underlying mechanisms. RESULTS Carotid arteries exposed to long-term oscillatory flow exhibited hyperplastic neointima, reduced endothelial continuity, and increased SMC-like cells and ECM, indicating superficial erosion-prone lesions. In addition, oscillatory flow significantly induced EndMT, whereas inhibition of EndMT ameliorated the formation of superficial erosion-prone lesions. Bioinformatic data analyses and in vitro studies showed a remarkable reduction in anti-EndMT KLF2 and KLF4 in a DNA methyltransferase (DNMT)-dependent manner, and the suppression of DNMTs attenuated oscillatory flow-induced EndMT and superficial erosion-prone lesions. CONCLUSIONS Chronic oscillatory flow causes superficial erosion-prone lesions by activating EndMT in a DNMT-dependent manner. Our findings highlight a promising therapeutic strategy for the prevention of superficial erosions.
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Affiliation(s)
- Caiying Tang
- Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Guoxia Shi
- Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Ruyi Jia
- Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Xueying Pei
- Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Chao Wang
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
- Department of Ultrasound, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhuo Du
- Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Song Li
- Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Pingping Wan
- Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Sibo Sun
- Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Cong Peng
- Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Shuang Li
- Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Ping Sun
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
- Department of Ultrasound, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Bo Yu
- Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
- The State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Harbin,China
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Jiannan Dai
- Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
- The State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Harbin,China
- The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
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7
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Pasterkamp G, den Ruijter HM, Mokry M. Plaque erosion: unmasking the complexity of atherosclerotic disease. Eur Heart J 2025:ehaf197. [PMID: 40200852 DOI: 10.1093/eurheartj/ehaf197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/10/2025] Open
Affiliation(s)
- Gerard Pasterkamp
- Central Diagnostics Laboratory, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands
| | - Hester M den Ruijter
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Michal Mokry
- Central Diagnostics Laboratory, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
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8
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Wang S, Luo X, Hu S, Zhao C, Sun Q, Zeng M, Bao X, Wang Y, Wu F, Yang Y, Lv Y, Bai X, Hao W, Liu M, Yi B, Chen Y, Meng W, Li J, Li M, Huang J, Wu T, Zhao Y, Zhang Z, An J, Libby P, Jia H, Yu B. Plaque erosion risk and JAK2 V617F variant. Eur Heart J 2025:ehaf114. [PMID: 40053703 DOI: 10.1093/eurheartj/ehaf114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 06/21/2024] [Accepted: 02/07/2025] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND AND AIMS Clonal haematopoiesis of indeterminate potential (CHIP) can increase the risk of myocardial infarction (MI). Among various CHIP mutations, JAK2 V617F substantially elevated this risk. However, the specific associations between JAK2 V617F and two mechanisms of MI, plaque erosion and plaque rupture, remain unclear. METHODS Case-control studies investigated these associations. A total of 728 erosion cases, 919 rupture cases, and 804 controls were included from our centre. Digital-drop polymerase chain reaction was performed on these individuals to identify the presence of JAK2 V617F. Previous experimental work has implicated neutrophils in the pathogenesis of erosion in the presence of this mutation. Thus, single-cell RNA sequencing of neutrophils from both JAK2 V617F carriers and healthy donors was performed to seek the potential mechanisms responsible for erosion associated with JAK2 V617F. RESULTS Among the participants, 26 (3.57%) erosion patients, 7 (.76%) rupture patients, and 3 (.37%) controls were identified as JAK2 V617F carriers with a variant allele frequency (VAF) ≥1%. The carriers among the erosion patients exhibited higher platelet counts and lower glycated haemoglobin and blood lipid levels. Logistic regression analysis, considering erosion or rupture as separate cases, revealed that JAK2 V617F carriers with a VAF ≥1% showed a significant association with erosion [odds ratio (OR) 16.246, 95% confidence interval (CI) 4.624-57.080, P < .0001], but not with rupture (OR 1.677, 95% CI .379-7.415, P = .495). Single-cell RNA-sequencing data indicated that neutrophils from JAK2 V617F carriers displayed augmented expression levels of genes and gene sets associated with activation, adhesion, migration, and granule secretion. CONCLUSIONS JAK2 V617F linked to a high risk of erosion, an association to which enhanced neutrophil activation may contribute.
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Affiliation(s)
- Shengfang Wang
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Department of Cardiology, Central China Fuwai Hospital of Zhengzhou University, Henan Provincial People's Hospital Heart Center, No. 1 Fuwai Avenue, Zhengdong New District, Zhengzhou, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Xing Luo
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Sining Hu
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Chen Zhao
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Qianhui Sun
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Ming Zeng
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Xiaoyi Bao
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Yini Wang
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Fangfang Wu
- College of Arts and Sciences, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, China
| | - Yeqiu Yang
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Ying Lv
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Xiaoxuan Bai
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Wei Hao
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Minghao Liu
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Boling Yi
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Yuwu Chen
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Wei Meng
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Ji Li
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Man Li
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Jianxin Huang
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Tianyu Wu
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Yipin Zhao
- Department of Cardiology, Central China Fuwai Hospital of Zhengzhou University, Henan Provincial People's Hospital Heart Center, No. 1 Fuwai Avenue, Zhengdong New District, Zhengzhou, China
| | - Zhulin Zhang
- Department of Cardiology, Shanxi Cardiovascular Hospital, No. 18 Yifen Street, Wanbailin District, Taiyuan, China
| | - Jian An
- Department of Cardiology, Shanxi Coal Central Hospital, No. 101 Xuefu Street, Xiaodian District, Taiyuan, China
| | - Peter Libby
- Division of Cardiovascular Medicine, Heart and Vascular Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Haibo Jia
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
| | - Bo Yu
- Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China
- Key Laboratory of Myocardial Ischemia, Ministry of Education, No. 246 Xuefu Road, Nangang District, Harbin 150001, China
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9
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Vergallo R, Park SJ, Stone GW, Erlinge D, Porto I, Waksman R, Mintz GS, D'Ascenzo F, Seitun S, Saba L, Vliegenthart R, Alfonso F, Arbab-Zadeh A, Libby P, Di Carli MF, Muller JE, Maurer G, Gropler RJ, Chandrashekhar YS, Braunwald E, Fuster V, Jang IK. Vulnerable or High-Risk Plaque: A JACC: Cardiovascular Imaging Position Statement. JACC Cardiovasc Imaging 2025:S1936-878X(25)00028-2. [PMID: 40019413 DOI: 10.1016/j.jcmg.2024.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 11/06/2024] [Accepted: 11/10/2024] [Indexed: 03/01/2025]
Abstract
The concept of high-risk plaque emerged from pathologic and epidemiologic studies 3 decades ago that demonstrated plaque rupture with thrombosis as the predominant mechanism of acute coronary syndrome and sudden cardiac death. Thin-cap fibroatheroma, a plaque with a large lipidic core covered by a thin fibrous cap, is the prototype of the rupture-prone plaque and has been traditionally defined as "vulnerable plaque." Although knowledge on the pathophysiology of plaque instability continues to grow, the risk profile of our patients has shifted and the character of atherosclerotic disease has evolved, partly because of widespread use of lipid-lowering therapies and other preventive measures. In vivo intracoronary imaging studies indicate that superficial erosion causes up to 40% of acute coronary syndromes. This changing landscape calls for broader perspective, expanding the concept of high-risk plaque to the precursors of all major substrates of coronary thrombosis beyond plaque rupture. Other factors to take into consideration include dynamic changes in plaque composition, the importance of plaque burden, inflammatory activation (both local and systemic), healing mechanisms, regional hemodynamic pattern, properties of the fluid phase of blood, and the amount of myocardium at risk subtended by a lesion. Rather than the traditional focus limited to the thin-cap fibroatheroma, the authors advocate a more comprehensive approach that considers both morphologic features and biological activity of plaques and blood. This position paper highlights the challenges to the usual concept of high-risk plaque, proposes a broader definition, and analyzes its key morphologic features, the technological progress of plaque imaging (particularly using intracoronary imaging techniques), advances in pharmacologic therapies for plaque regression and stabilization, and the feasibility and efficacy of focal interventional treatments including preemptive plaque sealing.
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Affiliation(s)
- Rocco Vergallo
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Università di Genova, Genoa, Italy
| | | | - Gregg W Stone
- Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | | | - Italo Porto
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Università di Genova, Genoa, Italy
| | - Ron Waksman
- MedStar Washington Hospital Center, Washington, District of Columbia, USA
| | - Gary S Mintz
- Cardiovascular Research Foundation, New York, New York, USA
| | | | - Sara Seitun
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Luca Saba
- University of Cagliari, Cagliari, Italy
| | | | - Fernando Alfonso
- Hospital Universitario La Princesa, CIBERCV, IIS-IP, Universidad Autónoma Madrid, Madrid, Spain
| | | | - Peter Libby
- Brigham and Women's Hospital, Boston, Massachusetts, USA
| | | | - James E Muller
- Brigham and Women's Hospital, Boston, Massachusetts, USA
| | | | - Robert J Gropler
- Washington University School of Medicine, St. Louis, Missouri, USA
| | | | | | - Valentin Fuster
- Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Ik-Kyung Jang
- Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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10
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Hebbo E, Khan S, Manzo-Silberman S, Alasnag M. The Clinical Approach to Angina in Women. Interv Cardiol Clin 2025; 14:1-8. [PMID: 39537281 DOI: 10.1016/j.iccl.2024.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Women presenting with angina are more likely to have cardiac chest pain accompanied more frequently by associated symptoms like abdominal pain and lightheadedness. The evaluation of women with suspected coronary disease can be complex because many have microvascular dysfunction, coronary vasospasm, and altered coagulation that require specific testing protocols beyond the conventional stress testing and a coronary angiogram. Therefore, terms such as angina, ischemia, and myocardial infarction with no obstructive coronary disease have been introduced in recent years. More studies are required to elaborate guidelines on the diagnosis and management of these entities.
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Affiliation(s)
- Elsa Hebbo
- Department of Medicine, Division of Cardiology, Emory University School of Medicine, Emory Heart and Vascular Center, Atlanta, GA, USA
| | - Sahoor Khan
- Interventional Cardiology Program, Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, MA, USA
| | | | - Mirvat Alasnag
- Cardiac Center, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia.
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11
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Hamana T, Shah P, Grogan A, Kawakami R, Williams D, Diaz KM, Virmani R, Finn AV. Risk Factors Favoring Plaque Erosion. Curr Atheroscler Rep 2024; 27:17. [PMID: 39661076 DOI: 10.1007/s11883-024-01262-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/25/2024] [Indexed: 12/12/2024]
Abstract
PURPOSE OF REVIEW Plaque erosion is the second leading cause of coronary thrombosis following plaque rupture and represents a key pathophysiological process underlying acute coronary syndromes that can culminate in sudden coronary death. While the precise mechanisms and risk factors driving plaque rupture are well-established, those for erosion have only recently been explored. This review summarizes current literature on the characteristics and risk factors favoring plaque erosion. RECENT FINDINGS Plaque erosion is characterized by a defective endothelial layer in the intima, promoting thrombus formation in the presence of an intact fibrous cap. It is more common in younger women (< 50 years) and smokers. Pathologic intimal thickening or fibroatheroma are common underlying lesions. Risk factors include gender, age, smoking, and disturbances in shear flow. Advances in pathogenic and molecular mechanisms, such as endothelial shear stress, neutrophil activation, and toll-like receptor-2 pathways, are discussed. Understanding the major risk factors for plaque erosion can inform diagnostics and therapeutics to prevent the progression of arterial thrombosis.
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Affiliation(s)
- Tomoyo Hamana
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, 20878, USA
| | - Palak Shah
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, 20878, USA
| | - Alyssa Grogan
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, 20878, USA
| | - Rika Kawakami
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, 20878, USA
| | - Desiree Williams
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, 20878, USA
| | | | - Renu Virmani
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, 20878, USA
| | - Aloke V Finn
- CVPath Institute, Inc, 19 Firstfield Road, Gaithersburg, MD, 20878, USA.
- School of Medicine, University of Maryland, Baltimore, MD, USA.
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12
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Lin S, Yu Y, Söderström LÅ, Gisterå A. Erosion of the Atheroma: Wicked T Cells at the Culprit Site. Curr Atheroscler Rep 2024; 27:4. [PMID: 39549205 PMCID: PMC11569023 DOI: 10.1007/s11883-024-01247-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/31/2024] [Indexed: 11/18/2024]
Abstract
PURPOSE OF REVIEW There is a growing recognition of plaque erosion as a cause of acute coronary syndrome. This review aims to examine the potential involvement of T cells in this process. RECENT FINDINGS Immune-vascular interactions have been identified in the development of plaque erosions. Up to one-third of eroded plaques show evidence of active immune infiltration, with the presence of T cells. We propose that microerosions may frequently occur in association with the infiltration of T cells and macrophages in early atherosclerotic lesions. Healing of erosions could trigger the deposition of excessive extracellular matrix. The pro-inflammatory and cytotoxic actions of T cells, along with reduced endothelial integrity and other mechanisms, may subsequently give rise to clinical symptoms. To gain a better understanding of the role of T cells in plaque erosion, it is crucial to develop improved models for conducting controlled experiments and to study atherosclerosis in younger individuals.
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Affiliation(s)
- Shiying Lin
- Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Yinda Yu
- Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Leif Å Söderström
- Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Anton Gisterå
- Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
- Karolinska University Hospital, Visionsgatan 4, Solna, Stockholm, SE-17164, Sweden.
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13
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Lee WE, Genetzakis E, Barsha G, Vescovi J, Mifsud C, Vernon ST, Nguyen TV, Gray MP, Grieve SM, Figtree GA. Expression of Myeloperoxidase in Patient-Derived Endothelial Colony-Forming Cells-Associations with Coronary Artery Disease and Mitochondrial Function. Biomolecules 2024; 14:1308. [PMID: 39456241 PMCID: PMC11505856 DOI: 10.3390/biom14101308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 10/06/2024] [Accepted: 10/14/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND AND AIMS Myeloperoxidase (MPO) plays a critical role in the innate immune response and has been suggested to be a surrogate marker of oxidative stress and inflammation, with elevated levels implicated in cardiovascular diseases, such as atherosclerosis and heart failure, as well as in conditions like rheumatoid arthritis and cancer. While MPO is well-known in leukocytes, its expression and function in human endothelial cells remain unclear. This study investigates MPO expression in patient-derived endothelial colony-forming cells (ECFCs) and its potential association with CAD and mitochondrial function. METHODS ECFCs were cultured from the peripheral blood of 93 BioHEART-CT patients. MPO expression and associated functions were examined using qRT-PCR, immunochemistry, flow cytometry, and MPO activity assays. CAD presence was defined using CT coronary angiography (CACS > 0). RESULTS We report MPO presence in patient-derived ECFCs for the first time. MPO protein expression occurred in 70.7% of samples (n = 41) which had nuclear co-localisation, an atypical observation given its conventional localisation in the granules of neutrophils and monocytes. This suggests potential alternative roles for MPO in nuclear processes. MPO mRNA expression was detected in 66.23% of samples (n = 77). CAD patients had a lower proportion of MPO-positive ECFCs compared to non-CAD controls (57.45% vs. 80%, p = 0.04), a difference that persisted in the statin-naïve sub-cohort (53.85% vs. 84.62%, p = 0.02). Non-CAD patients with MPO expression showed upregulated mitochondrial-antioxidant genes (AIFM2, TXNRD1, CAT, PRDX3, PRDX6). In contrast, CAD patients with MPO gene expression had heightened mROS production and mitochondrial mass and decreased mitochondrial function compared to that of CAD patients without MPO gene expression. CONCLUSIONS MPO is present in the nucleus of ECFCs. In non-CAD ECFCs, MPO expression is linked to upregulated mitochondrial-antioxidant genes, whereas in CAD ECFCs, it is associated with greater mitochondrial dysfunction.
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Affiliation(s)
- Weiqian Eugene Lee
- Kolling Institute, 10 Westbourne Street, St Leonards, Sydney, NSW 2064, Australia
| | - Elijah Genetzakis
- Kolling Institute, 10 Westbourne Street, St Leonards, Sydney, NSW 2064, Australia
| | - Giannie Barsha
- The Victorian Heart Institute and Biomedicine Discovery Institute, Monash University, Wellington Road, Clayton, Melbourne, VIC 3800, Australia
| | - Joshua Vescovi
- Kolling Institute, 10 Westbourne Street, St Leonards, Sydney, NSW 2064, Australia
| | - Carmen Mifsud
- Kolling Institute, 10 Westbourne Street, St Leonards, Sydney, NSW 2064, Australia
| | - Stephen T. Vernon
- Kolling Institute, 10 Westbourne Street, St Leonards, Sydney, NSW 2064, Australia
| | - Tung Viet Nguyen
- Kolling Institute, 10 Westbourne Street, St Leonards, Sydney, NSW 2064, Australia
| | - Michael P. Gray
- Kolling Institute, 10 Westbourne Street, St Leonards, Sydney, NSW 2064, Australia
| | - Stuart M. Grieve
- Charles Perkins Centre, Johns Hopkins Drive, Camperdown, Sydney, NSW 2050, Australia
| | - Gemma A. Figtree
- Kolling Institute, 10 Westbourne Street, St Leonards, Sydney, NSW 2064, Australia
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14
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Volleberg RHJA, Mol JQ, Belkacemi A, Hermanides RS, Meuwissen M, Protopopov AV, Laanmets P, Krestyaninov OV, Dennert R, Oemrawsingh RM, van Kuijk JP, Arkenbout K, van der Heijden DJ, Rasoul S, Lipsic E, Rodwell L, Camaro C, Damman P, Roleder T, Kedhi E, van Leeuwen MAH, van Geuns RJM, van Royen N. Sex differences in plaque characteristics of fractional flow reserve-negative non-culprit lesions after myocardial infarction. Atherosclerosis 2024; 397:118568. [PMID: 39241345 DOI: 10.1016/j.atherosclerosis.2024.118568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 07/12/2024] [Accepted: 08/21/2024] [Indexed: 09/09/2024]
Abstract
BACKGROUND AND AIMS Recurrent events after myocardial infarction (MI) are common and often originate from native non-culprit (NC) lesions that are non-flow limiting. These lesions consequently pose as targets to improve long-term outcome. It is, however, largely unknown whether these lesions differ between sexes. The aim of this study was to assess such potential differences. METHODS From the PECTUS-obs study, we assessed sex-related differences in plaque characteristics of fractional flow reserve (FFR)-negative intermediate NC lesions in 420 MI-patients. RESULTS Among the included patients, 80 (19.1 %) were female and 340 (80.9 %) male. Women were older and more frequently had hypertension and diabetes. In total, 494 NC lesions were analyzed. After adjustment for clinical characteristics and accounting for within-patients clustering, lesion length was longer in female patients (20.8 ± 10.0 vs 18.3 ± 8.5 mm, p = 0.048) and minimum lumen area (2.30 ± 1.42 vs 2.78 ± 1.54 mm2, p < 0.001) and minimum lumen diameter (1.39 ± 0.45 vs 1.54 ± 0.44 mm, p < 0.001) were smaller. The minimum fibrous cap thickness was smaller among females (96 ± 53 vs 112 ± 72 μm, p = 0.025), with more lesions harboring a thin cap fibroatheroma (39.3 % vs 24.9 %, p < 0.001). Major adverse cardiovascular events at two years occurred in 6.3 % of female patients and 11.8 % of male patients (p = 0.15). CONCLUSIONS FFR-negative NC lesions after MI harbored more high-risk plaque features in female patients. Although this did not translate into an excess of recurrent events in female patients in this modestly sized cohort, it remains to be investigated whether this difference affects clinical outcome.
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Affiliation(s)
- Rick H J A Volleberg
- Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Jan-Quinten Mol
- Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands
| | | | | | | | - Alexey V Protopopov
- Cardiovascular Center of Regional State Hospital, Krasnoyarsk, Russia; Krasnoyarsk State Medical University, Krasnoyarsk, Russia
| | - Peep Laanmets
- Cardiology Center, North Estonia Medical Center, Tallinn, Estonia
| | | | - Robert Dennert
- Department of Cardiology, Dr. Horacio E. Oduber Hospital, Oranjestad, Aruba
| | - Rohit M Oemrawsingh
- Department of Cardiology, Amphia Hospital, Breda, the Netherlands; Department of Cardiology, Albert Schweitzer Hospital, Dordrecht, the Netherlands
| | - Jan-Peter van Kuijk
- Department of Cardiology, Sint Antonius Hospital, Nieuwegein, the Netherlands
| | - Karin Arkenbout
- Department of Cardiology, Tergooi Hospital, Blaricum, the Netherlands
| | - Dirk J van der Heijden
- Department of Cardiology, Isala Hospital, Zwolle, the Netherlands; Department of Cardiology, Haaglanden Medical Center, The Hague, the Netherlands
| | - Saman Rasoul
- Department of Cardiology, Zuyderland Medical Center, Heerlen, the Netherlands; Department of Cardiology, MUMC+, Maastricht, the Netherlands
| | - Erik Lipsic
- Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands
| | - Laura Rodwell
- Department of Epidemiology, Biostatistics and Health Technology Assessment, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Cyril Camaro
- Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Peter Damman
- Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Tomasz Roleder
- Faculty of Medicine Wrocław University of Science and Technology, Department of Cardiology, Regional Specialist Hospital, Wrocław, Poland
| | - Elvin Kedhi
- Department of Cardiology, McGill University Health Center, Royal Victoria Hospital, Montreal, Canada
| | | | | | - Niels van Royen
- Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.
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15
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Buonpane A, Trimarchi G, Ciardetti M, Coceani MA, Alagna G, Benedetti G, Berti S, Andò G, Burzotta F, De Caterina AR. Optical Coherence Tomography in Myocardial Infarction Management: Enhancing Precision in Percutaneous Coronary Intervention. J Clin Med 2024; 13:5791. [PMID: 39407851 PMCID: PMC11477163 DOI: 10.3390/jcm13195791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 09/23/2024] [Accepted: 09/27/2024] [Indexed: 10/20/2024] Open
Abstract
In acute myocardial infarction (AMI), the urgency of coronary revascularization through percutaneous coronary intervention (PCI) is paramount, offering notable advantages over pharmacologic treatment. However, the persistent risk of adverse events, including recurrent AMI and heart failure post-revascularization, underscores the necessity for enhanced strategies in managing coronary artery disease. Traditional angiography, while widely employed, presents significant limitations by providing only two-dimensional representations of complex three-dimensional vascular structures, hampering the accurate assessment of plaque characteristics and stenosis severity. Intravascular imaging, specifically optical coherence tomography (OCT), significantly addresses these limitations with superior spatial resolution compared to intravascular ultrasound (IVUS). Within the context of AMI, OCT serves dual purposes: as a diagnostic tool to accurately identify culprit lesions in ambiguous cases and as a guide for optimizing PCI procedures. Its capacity to differentiate between various mechanisms of acute coronary syndrome, such as plaque rupture and spontaneous coronary dissection, enhances its diagnostic potential. Furthermore, OCT facilitates precise lesion preparation, optimal stent sizing, and confirms stent deployment efficacy. Recent meta-analyses indicate that OCT-guided PCI markedly improves safety and efficacy in revascularization, subsequently decreasing the risks of mortality and complications. This review emphasizes the critical role of OCT in refining patient-specific therapeutic approaches, aligning with the principles of precision medicine to enhance clinical outcomes for individuals experiencing AMI.
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Affiliation(s)
- Angela Buonpane
- Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Rome, Largo Agostino Gemelli, 1, 00168 Roma, Italy; (A.B.); (F.B.)
| | - Giancarlo Trimarchi
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy; (G.T.); (G.A.)
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant’Anna, 56127 Pisa, Italy
| | - Marco Ciardetti
- Cardiology and Pneumology Division, Fondazione Toscana G. Monasterio, 56124 Pisa, Italy; (M.C.); (M.A.C.)
| | - Michele Alessandro Coceani
- Cardiology and Pneumology Division, Fondazione Toscana G. Monasterio, 56124 Pisa, Italy; (M.C.); (M.A.C.)
| | - Giulia Alagna
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy; (G.T.); (G.A.)
| | - Giovanni Benedetti
- Fondazione Toscana G. Monasterio, Ospedale del Cuore G., Pasquinucci, 54100 Massa, Italy; (G.B.); (S.B.); (A.R.D.C.)
| | - Sergio Berti
- Fondazione Toscana G. Monasterio, Ospedale del Cuore G., Pasquinucci, 54100 Massa, Italy; (G.B.); (S.B.); (A.R.D.C.)
| | - Giuseppe Andò
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy; (G.T.); (G.A.)
| | - Francesco Burzotta
- Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Rome, Largo Agostino Gemelli, 1, 00168 Roma, Italy; (A.B.); (F.B.)
| | - Alberto Ranieri De Caterina
- Fondazione Toscana G. Monasterio, Ospedale del Cuore G., Pasquinucci, 54100 Massa, Italy; (G.B.); (S.B.); (A.R.D.C.)
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16
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Lee J, Gharaibeh Y, Zimin VN, Kim JN, Hassani NS, Dallan LAP, Pereira GTR, Makhlouf MHE, Hoori A, Wilson DL. Plaque Characteristics Derived from Intravascular Optical Coherence Tomography That Predict Cardiovascular Death. Bioengineering (Basel) 2024; 11:843. [PMID: 39199801 PMCID: PMC11351967 DOI: 10.3390/bioengineering11080843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 08/14/2024] [Accepted: 08/16/2024] [Indexed: 09/01/2024] Open
Abstract
This study aimed to investigate whether plaque characteristics derived from intravascular optical coherence tomography (IVOCT) could predict a long-term cardiovascular (CV) death. This study was a single-center, retrospective study on 104 patients who had undergone IVOCT-guided percutaneous coronary intervention. Plaque characterization was performed using Optical Coherence TOmography PlaqUe and Stent (OCTOPUS) software developed by our group. A total of 31 plaque features, including lesion length, lumen, calcium, fibrous cap (FC), and vulnerable plaque features (e.g., microchannel), were computed from the baseline IVOCT images. The discriminatory power for predicting CV death was determined using univariate/multivariate logistic regressions. Of 104 patients, CV death was identified in 24 patients (23.1%). Univariate logistic regression revealed that lesion length, calcium angle, calcium thickness, FC angle, FC area, and FC surface area were significantly associated with CV death (p < 0.05). In the multivariate logistic analysis, only the FC surface area (OR 2.38, CI 0.98-5.83, p < 0.05) was identified as a significant determinant for CV death, highlighting the importance of the 3D lesion analysis. The AUC of FC surface area for predicting CV death was 0.851 (95% CI 0.800-0.927, p < 0.05). Patients with CV death had distinct plaque characteristics (i.e., large FC surface area) in IVOCT. Studies such as this one might someday lead to recommendations for pharmaceutical and interventional approaches.
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Affiliation(s)
- Juhwan Lee
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; (J.L.); (J.N.K.); (A.H.)
| | - Yazan Gharaibeh
- Department of Biomedical Engineering, Faculty of Engineering, The Hashemite University, Zarqa 13133, Jordan;
| | - Vladislav N. Zimin
- Brookdale University Hospital Medical Center, 1 Brookdale Plaza, Brooklyn, NY 11212, USA;
| | - Justin N. Kim
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; (J.L.); (J.N.K.); (A.H.)
| | - Neda S. Hassani
- Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA; (N.S.H.); (L.A.P.D.); (G.T.R.P.); (M.H.E.M.)
| | - Luis A. P. Dallan
- Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA; (N.S.H.); (L.A.P.D.); (G.T.R.P.); (M.H.E.M.)
| | - Gabriel T. R. Pereira
- Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA; (N.S.H.); (L.A.P.D.); (G.T.R.P.); (M.H.E.M.)
| | - Mohamed H. E. Makhlouf
- Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA; (N.S.H.); (L.A.P.D.); (G.T.R.P.); (M.H.E.M.)
| | - Ammar Hoori
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; (J.L.); (J.N.K.); (A.H.)
| | - David L. Wilson
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; (J.L.); (J.N.K.); (A.H.)
- Department of Radiology, Case Western Reserve University, Cleveland, OH 44106, USA
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17
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Annink ME, Kraaijenhof JM, Stroes ESG, Kroon J. Moving from lipids to leukocytes: inflammation and immune cells in atherosclerosis. Front Cell Dev Biol 2024; 12:1446758. [PMID: 39161593 PMCID: PMC11330886 DOI: 10.3389/fcell.2024.1446758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 07/22/2024] [Indexed: 08/21/2024] Open
Abstract
Atherosclerotic cardiovascular disease (ASCVD) is the most important cause of morbidity and mortality worldwide. While it is traditionally attributed to lipid accumulation in the vascular endothelium, recent research has shown that plaque inflammation is an important additional driver of atherogenesis. Though clinical outcome trials utilizing anti-inflammatory agents have proven promising in terms of reducing ASCVD risk, it is imperative to identify novel actionable targets that are more specific to atherosclerosis to mitigate adverse effects associated with systemic immune suppression. To that end, this review explores the contributions of various immune cells from the innate and adaptive immune system in promoting and mitigating atherosclerosis by integrating findings from experimental studies, high-throughput multi-omics technologies, and epidemiological research.
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Affiliation(s)
- Maxim E. Annink
- Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - Jordan M. Kraaijenhof
- Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - Erik S. G. Stroes
- Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - Jeffrey Kroon
- Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
- Department of Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
- Laboratory of Angiogenesis and Vascular Metabolism, VIB-KU Leuven Center for Cancer Biology, Leuven, Belgium
- Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium
- Amsterdam Cardiovascular Sciences, Atherosclerosis and Ischemic Syndromes, Amsterdam, Netherlands
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18
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Diez Benavente E, Sakkers TR, van der Harst P, den Ruijter HM. Atherosclerotic plaque-specific methylation biomarkers in plasma cell-free DNA of female and male patients with coronary artery disease. Eur Heart J 2024; 45:2468-2470. [PMID: 38685672 DOI: 10.1093/eurheartj/ehae156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/02/2024] Open
Affiliation(s)
- Ernest Diez Benavente
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Tim R Sakkers
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Pim van der Harst
- Department of Cardiology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Hester M den Ruijter
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
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19
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Kawai K, Kawakami R, Finn AV, Virmani R. Differences in Stable and Unstable Atherosclerotic Plaque. Arterioscler Thromb Vasc Biol 2024; 44:1474-1484. [PMID: 38924440 DOI: 10.1161/atvbaha.124.319396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/28/2024]
Affiliation(s)
- Kenji Kawai
- Department of Pathology, CVPath Institute, Gaithersburg, MD (K.K., R.K., A.V.F., R.V.)
| | - Rika Kawakami
- Department of Pathology, CVPath Institute, Gaithersburg, MD (K.K., R.K., A.V.F., R.V.)
| | - Aloke V Finn
- Department of Pathology, CVPath Institute, Gaithersburg, MD (K.K., R.K., A.V.F., R.V.)
- University of Maryland School of Medicine, Baltimore (A.V.F.)
| | - Renu Virmani
- Department of Pathology, CVPath Institute, Gaithersburg, MD (K.K., R.K., A.V.F., R.V.)
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20
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Bulnes JF, González L, Velásquez L, Orellana MP, Venturelli PM, Martínez G. Role of inflammation and evidence for the use of colchicine in patients with acute coronary syndrome. Front Cardiovasc Med 2024; 11:1356023. [PMID: 38993522 PMCID: PMC11236697 DOI: 10.3389/fcvm.2024.1356023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 05/29/2024] [Indexed: 07/13/2024] Open
Abstract
Acute Coronary Syndrome (ACS) significantly contributes to cardiovascular death worldwide. ACS may arise from the disruption of an atherosclerotic plaque, ultimately leading to acute ischemia and myocardial infarction. In the pathogenesis of atherosclerosis, inflammation assumes a pivotal role, not solely in the initiation and complications of atherosclerotic plaque formation, but also in the myocardial response to ischemic insult. Acute inflammatory processes, coupled with time to reperfusion, orchestrate ischemic and reperfusion injuries, dictating infarct magnitude and acute left ventricular (LV) remodeling. Conversely, chronic inflammation, alongside neurohumoral activation, governs persistent LV remodeling. The interplay between chronic LV remodeling and recurrent ischemic episodes delineates the progression of the disease toward heart failure and cardiovascular death. Colchicine exerts anti-inflammatory properties affecting both the myocardium and atherosclerotic plaque by modulating the activity of monocyte/macrophages, neutrophils, and platelets. This modulation can potentially result in a more favorable LV remodeling and forestalls the recurrence of ACS. This narrative review aims to delineate the role of inflammation across the different phases of ACS pathophysiology and describe the mechanistic underpinnings of colchicine, exploring its purported role in modulating each of these stages.
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Affiliation(s)
- Juan Francisco Bulnes
- División de Enfermedades Cardiovasculares, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Leticia González
- Centro de Imágenes Biomédicas, Departamento de Radiología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Leonardo Velásquez
- División de Enfermedades Cardiovasculares, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - María Paz Orellana
- División de Enfermedades Cardiovasculares, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Paula Muñoz Venturelli
- Centro de Estudios Clínicos, Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
| | - Gonzalo Martínez
- División de Enfermedades Cardiovasculares, Pontificia Universidad Católica de Chile, Santiago, Chile
- Heart Research Institute, Sydney, NSW, Australia
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21
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Fukase T, Dohi T. Visualization of Vulnerable Coronary Plaque and Prevention of Plaque Rupture. JUNTENDO IJI ZASSHI = JUNTENDO MEDICAL JOURNAL 2024; 70:260-268. [PMID: 39431179 PMCID: PMC11487368 DOI: 10.14789/jmj.jmj24-0011-r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 03/25/2024] [Indexed: 10/22/2024]
Abstract
In daily clinical practice, assessing anatomical findings and the presence or absence of ischemia is pivotal for determining the need for percutaneous coronary intervention. However, concurrently, comprehending vulnerability can greatly assist in predicting future cardiovascular events and formulating preventive strategies for individual patients. This review aims to describe the vulnerability of coronary artery plaques, primarily focusing on vulnerable plaques through pathological, morphological, and physiological viewpoints. Our review emphasizes the usefulness of coronary imaging modalities for the diagnosis of vulnerable plaques and the assessment of their rupture risk, as well as the possibility of percutaneous coronary intervention as a management strategy for plaque stabilization. Our findings show that there have been sporadic accounts of the potential of preventing cardiovascular events through early invasive treatments in patients with moderate or greater ischemia and utilizing new-generation stents to seal lipid core plaques. Thus, it is anticipated that direct intervention targeting coronary plaques, coupled with strict low-density lipoprotein-cholesterol lowering therapy, can play a vital role in suppressing future cardiovascular events and archiving zero perioperative myocardial infarction.
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22
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Bruoha S, Galli M, Sabouret P, Yosefy C, Taha L, Gragnano F, Savage MP, Shuvy M, Biondi-Zoccai G, Glikson M, Asher E. Atherosclerotic Plaque Erosion: Mechanisms, Clinical Implications, and Potential Therapeutic Strategies-A Review. J Cardiovasc Pharmacol 2024; 83:547-556. [PMID: 38421206 DOI: 10.1097/fjc.0000000000001554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 02/13/2024] [Indexed: 03/02/2024]
Abstract
Atherosclerosis is an insidious and progressive inflammatory disease characterized by the formation of lipid-laden plaques within the intima of arterial walls with potentially devastating consequences. While rupture of vulnerable plaques has been extensively studied, a distinct mechanism known as plaque erosion (PE) has gained recognition and attention in recent years. PE, characterized by the loss of endothelial cell lining in the presence of intact fibrous cap, contributes to a significant and growing proportion of acute coronary events. However, despite a heterogeneous substrate underlying coronary thrombosis, treatment remains identical. This article provides an overview of atherosclerotic PE characteristics and its underlying mechanisms, highlights its clinical implications, and discusses potential therapeutic strategies.
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Affiliation(s)
- Sharon Bruoha
- Department of Cardiology, Barzilai Medical Center, the Ben-Gurion University of the Negev, Israel
| | - Mattia Galli
- Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy
| | - Pierre Sabouret
- Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy
- National College of French Cardiologists, 13 rue Niepce, 75014 Paris, France
| | - Chaim Yosefy
- Department of Cardiology, Barzilai Medical Center, the Ben-Gurion University of the Negev, Israel
| | - Louay Taha
- Jesselson Integrated Heart Center, Shaare Zedek Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel
| | - Felice Gragnano
- Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", Caserta, Italy
- Division of Clinical Cardiology, A.O.R.N. "Sant'Anna e San Sebastiano", Caserta, Italy
| | - Michael P Savage
- Division of Cardiology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Mony Shuvy
- Jesselson Integrated Heart Center, Shaare Zedek Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel
| | - Giuseppe Biondi-Zoccai
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy ; and
- Mediterranea Cardiocentro, Naples, Italy
| | - Michael Glikson
- Jesselson Integrated Heart Center, Shaare Zedek Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel
| | - Elad Asher
- Jesselson Integrated Heart Center, Shaare Zedek Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel
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23
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Zilio F, Musella F, Ceriello L, Ciliberti G, Pavan D, Manes MT, Selimi A, Scicchitano P, Iannopollo G, Albani S, Fortuni F, Grimaldi M, Colivicchi F, Oliva F. Sex differences in patients presenting with acute coronary syndrome: a state-of-the-art review. Curr Probl Cardiol 2024; 49:102486. [PMID: 38428554 DOI: 10.1016/j.cpcardiol.2024.102486] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Accepted: 02/22/2024] [Indexed: 03/03/2024]
Abstract
Cardiovascular conditions in the spectrum of acute coronary syndromes are characterized by sex differences with regard to pathophysiology, risk factors, clinical presentation, invasive and pharmacologic treatment, and outcomes. This review delves into these differences, including specific subsets like myocardial infarction with non-obstructed coronary arteries or Spontaneous Coronary Artery Dissection, and alternative diagnoses like Takotsubo cardiomyopathy or myocarditis. Moreover, practical considerations are enclosed, on how a sex-specific approach should be integrated in clinical practice: in fact, personal history should focus on female-specific risk factors, and hormonal status and hormonal therapy should be assessed. Moreover, physical and psychological stressors should be investigated, particularly in the event of Spontaneous Coronary Artery Dissection or Takotsubo cardiomyopathy.
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Affiliation(s)
- Filippo Zilio
- Department of Cardiology, Santa Chiara Hospital, APSS, 2, Largo Medaglie d'Oro, Trento 38123, Italy.
| | - Francesca Musella
- Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Cardiology Department, Santa Maria delle Grazie Hospital, Naples, Italy
| | - Laura Ceriello
- Cardiology Department, Ospedale Civile G. Mazzini, Teramo, Italy
| | - Giuseppe Ciliberti
- Cardiology and Arrhythmology Clinic, Marche University Hospital, Ancona, Italy
| | - Daniela Pavan
- Cardiology Unit, Azienda Sanitaria "Friuli Occidentale", Pordenone, Italy
| | | | - Adelina Selimi
- Cardiology and Arrhythmology Clinic, Marche University Hospital, Ancona, Italy
| | | | - Gianmarco Iannopollo
- Department of Cardiology, Maggiore Hospital Carlo Alberto Pizzardi, Bologna, Italy
| | - Stefano Albani
- Division of Cardiology, U. Parini Hospital, Aosta, Italy; Cardiovascular Institute Paris Sud, Massy, France
| | - Federico Fortuni
- Department of Cardiology, San Giovanni Battista Hospital, Foligno, Italy; Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Massimo Grimaldi
- Department of Cardiology, General Regional Hospital "F. Miulli", Bari, Italy
| | - Furio Colivicchi
- Clinical and Rehabilitation Cardiology Unit, San Filippo Neri Hospital, Rome, Italy
| | - Fabrizio Oliva
- Cardiologia 1, A. De Gasperis Cardicocenter, ASST Niguarda, Milan, Italy
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24
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Homma S, Kato K. Validity of Atherosclerotic Calcified Lesions Observed on Low-Dose Computed Tomography and Cardio-Ankle Vascular Index as Surrogate Markers of Atherosclerosis Progression. Angiology 2024; 75:349-358. [PMID: 36787785 DOI: 10.1177/00033197231155963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
Abstract
The significance of atherosclerotic calcified lesions observed on low-dose computed tomography (LDCT) performed during general checkups was investigated. The coronary arteries (CA), ascending aorta and aortic arch (AAAA), descending thoracic aorta (DTA), and abdominal aorta (AA) were examined. Semiquantitative calcified index analysis of the DTA and AA in terms of atherosclerosis risk factors and cardio-ankle vascular index (CAVI) measurements was also performed. We included 1594 participants (mean age: 59.2 years; range: 31-91 years). The prevalence of calcified lesions was 71.0%, 66.6%, 57.2%, and 37.9% in the AA, CA, AAAA, and DTA, respectively. Age-related advances in calcification among participants with no major risk factors, revealed that calcification appeared earliest in the AA, followed by the CA, AAAA, and DTA. Participants with calcified lesions in all arteries had a significantly greater CAVI than those without calcification. The CAVI was negatively correlated with low-density lipoprotein cholesterol levels, particularly in participants without calcified lesions in the DTA. Calcified lesions on LDCT could indicate the end stage of atherosclerotic lesions. The CAVI can be used to assess atherosclerotic changes at all stages of disease progression. A combination of LDCT and CAVI could be used as a routine non-invasive assessment of atherosclerosis.
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Affiliation(s)
- Satoki Homma
- Health Care Center in Saitama Medical Center of the Japan Community Health Care Organization, Saitama, Japan
- Faculty of Nursing and Medical Care, Keio University & Keio Research Institute at SFC (Shonan Fujisawa Campus), Fujisawa, Japan
| | - Kiyoe Kato
- Center of General Health Check-Up, Saiseikai Central Hospital, Tokyo, Japan
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25
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Mori H, Sekimoto T, Arai T, Sakai R, Sato S, Tezuka T, Omura A, Shinke T, Suzuki H. Mechanisms of Very Late Stent Thrombosis in Japanese Patients as Assessed by Optical Coherence Tomography. Can J Cardiol 2024; 40:696-704. [PMID: 38043704 DOI: 10.1016/j.cjca.2023.11.034] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Revised: 10/26/2023] [Accepted: 11/24/2023] [Indexed: 12/05/2023] Open
Abstract
BACKGROUND Although very late stent thrombosis (VLST) remains an important concern, the underlying etiology and clinical characteristics are not fully elucidated in Japanese patients who undergo intravascular imaging-guided percutaneous coronary intervention (PCI) regularly. METHODS We identified 50 VLST lesions (bare-metal stent [BMS] [n = 16], first-generation drug-eluting stent [DES] [n = 14] and newer-generation DES [n = 20]) in patients managed in our institutes. The underlying mechanism of VLST was assessed by optical coherence tomography (OCT), and the major etiology of each lesion was determined. The aim of this study was to explore the mechanisms of VLST of BMSs and DESs in Japanese patients. RESULTS The median duration since stent implantation was 10 years (range: 1-20). The most frequent etiology of VLST was neoatherosclerotic rupture (44%), followed by neointimal erosion (24%). Edge disease (10%) and evagination (10%) were similarly observed. Malapposition (8%) was deemed to be acquired late by looking at intravascular imaging from the index procedure. Uncovered struts (2%) and in-stent calcified nodule (2%) were the least frequent etiologies. Regardless of etiology, signs of neoatherosclerosis were present in most lesions (82%). Most patients received single (68%) or dual (8%) antiplatelet therapy or oral anticoagulation alone (4%), whereas a considerable proportion of patients discontinued medication (20%). Regarding the treatment strategy, drug-coated balloon was the most frequent strategy (56%), followed by implantation of newer DESs (34%). CONCLUSIONS Various mechanisms have been identified in Japanese patients with VLST. In these patients, biological responses seemed to be more relevant than the index procedure-related factors.
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Affiliation(s)
- Hiroyoshi Mori
- Showa University Fujigaoka Hospital, Yokohama, Kanagawa, Japan.
| | - Teruo Sekimoto
- Showa University Fujigaoka Hospital, Yokohama, Kanagawa, Japan
| | - Taito Arai
- Showa University Hospital, Shinagawa, Tokyo, Japan
| | - Rikuo Sakai
- Showa University Hospital, Shinagawa, Tokyo, Japan
| | - Shunya Sato
- Showa University Hospital, Shinagawa, Tokyo, Japan
| | - Takahiro Tezuka
- Showa University Fujigaoka Hospital, Yokohama, Kanagawa, Japan
| | - Ayumi Omura
- Showa University Fujigaoka Hospital, Yokohama, Kanagawa, Japan
| | | | - Hiroshi Suzuki
- Showa University Fujigaoka Hospital, Yokohama, Kanagawa, Japan
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26
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Pompei G, van de Hoef TP, den Ruijter HM, Kunadian V. Reading 2023 ESC ACS guidelines between the lines: Gaps in evidence in women. Eur J Clin Invest 2024; 54:e14148. [PMID: 38057949 DOI: 10.1111/eci.14148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 11/28/2023] [Accepted: 11/29/2023] [Indexed: 12/08/2023]
Affiliation(s)
- Graziella Pompei
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Tim P van de Hoef
- Division Heart and Lung, Department of Cardiology, University Medical Centre Utrecht, Utrecht, the Netherlands
| | - Hester M den Ruijter
- Laboratory of Experimental Cardiology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Vijay Kunadian
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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27
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Seppelt C, Abdelwahed YS, Meteva D, Nelles G, Stähli BE, Erbay A, Kränkel N, Sieronski L, Skurk C, Haghikia A, Sinning D, Dreger H, Knebel F, Trippel TD, Krisper M, Gerhardt T, Rai H, Klotsche J, Joner M, Landmesser U, Leistner DM. Coronary microevaginations characterize culprit plaques and their inflammatory microenvironment in a subtype of acute coronary syndrome with intact fibrous cap: results from the prospective translational OPTICO-ACS study. Eur Heart J Cardiovasc Imaging 2024; 25:175-184. [PMID: 37395586 DOI: 10.1093/ehjci/jead154] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 05/21/2023] [Accepted: 06/20/2023] [Indexed: 07/04/2023] Open
Abstract
AIMS Coronary microevaginations (CMEs) represent an outward bulge of coronary plaques and have been introduced as a sign of adverse vascular remodelling following coronary device implantation. However, their role in atherosclerosis and plaque destabilization in the absence of coronary intervention is unknown. This study aimed to investigate CME as a novel feature of plaque vulnerability and to characterize its associated inflammatory cell-vessel-wall interactions. METHODS AND RESULTS A total of 557 patients from the translational OPTICO-ACS study programme underwent optical coherence tomography imaging of the culprit vessel and simultaneous immunophenotyping of the culprit lesion (CL). Two hundred and fifty-eight CLs had a ruptured fibrous cap (RFC) and one hundred had intact fibrous cap (IFC) acute coronary syndrome (ACS) as an underlying pathophysiology. CMEs were significantly more frequent in CL when compared with non-CL (25 vs. 4%, P < 0.001) and were more frequently observed in lesions with IFC-ACS when compared with RFC-ACS (55.0 vs. 12.7%, P < 0.001). CMEs were particularly prevalent in IFC-ACS-causing CLs independent of a coronary bifurcation (IFC-ICB) when compared with IFC-ACS with an association to a coronary bifurcation (IFC-ACB, 65.4 vs. 43.7%, P = 0.030). CME emerged as the strongest independent predictor of IFC-ICB (relative risk 3.36, 95% confidence interval 1.67-6.76, P = 0.001) by multivariable regression analysis. IFC-ICB demonstrated an enrichment of monocytes in both culprit blood analysis (culprit ratio: 1.1 ± 0.2 vs. 0.9 ± 0.2, P = 0.048) and aspirated culprit thrombi (326 ± 162 vs. 96 ± 87 cells/mm2, P = 0.017), while IFC-ACB confirmed the accumulation of CD4+ T cells, as recently described. CONCLUSION This study provides novel evidence for a pathophysiological involvement of CME in the development of IFC-ACS and provides first evidence for a distinct pathophysiological pathway for IFC-ICB, driven by CME-derived flow disturbances and inflammatory activation involving the innate immune system. TRIAL REGISTRATION Registration of the study at clinicalTrials.gov (NCT03129503).
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Affiliation(s)
- Claudio Seppelt
- Department of Cardiology, University Heart Centre Berlin and Charité University Medicine Berlin, Campus Benjamin-Franklin (CBF), Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
| | - Youssef S Abdelwahed
- Department of Cardiology, University Heart Centre Berlin and Charité University Medicine Berlin, Campus Benjamin-Franklin (CBF), Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
| | - Denitsa Meteva
- Department of Cardiology, University Heart Centre Berlin and Charité University Medicine Berlin, Campus Benjamin-Franklin (CBF), Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
| | - Gregor Nelles
- Department of Cardiology, University Heart Centre Berlin and Charité University Medicine Berlin, Campus Benjamin-Franklin (CBF), Berlin 12203, Germany
| | - Barbara E Stähli
- Department of Cardiology, University Heart Centre Berlin and Charité University Medicine Berlin, Campus Benjamin-Franklin (CBF), Berlin 12203, Germany
| | - Aslihan Erbay
- Department of Cardiology, University Heart Centre Berlin and Charité University Medicine Berlin, Campus Benjamin-Franklin (CBF), Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
| | - Nicolle Kränkel
- Department of Cardiology, University Heart Centre Berlin and Charité University Medicine Berlin, Campus Benjamin-Franklin (CBF), Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
| | - Lara Sieronski
- Department of Cardiology, University Heart Centre Berlin and Charité University Medicine Berlin, Campus Benjamin-Franklin (CBF), Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
| | - Carsten Skurk
- Department of Cardiology, University Heart Centre Berlin and Charité University Medicine Berlin, Campus Benjamin-Franklin (CBF), Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
| | - Arash Haghikia
- Department of Cardiology, University Heart Centre Berlin and Charité University Medicine Berlin, Campus Benjamin-Franklin (CBF), Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
- Berlin Institute of Health (BIH), 10117 Berlin, Germany
| | - David Sinning
- Department of Cardiology, University Heart Centre Berlin and Charité University Medicine Berlin, Campus Benjamin-Franklin (CBF), Berlin 12203, Germany
| | - Henryk Dreger
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
- Department of Cardiology Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Fabian Knebel
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
- Department of Cardiology Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Department of Cardiology, Sana Klinikum Lichtenberg, Berlin, Germany
| | - Tobias D Trippel
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
- Department of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Berlin 13353, Germany
| | - Maximilian Krisper
- Department of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Berlin 13353, Germany
| | - Teresa Gerhardt
- Department of Cardiology, University Heart Centre Berlin and Charité University Medicine Berlin, Campus Benjamin-Franklin (CBF), Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
- Berlin Institute of Health (BIH), 10117 Berlin, Germany
| | - Himanshu Rai
- Department of Cardiology and ISAR Research Centre, German Heart Centre, Technical University Munich, Munich 80636, Germany
- Cardiovascular Research Institute Dublin, Imaging Core Lab, Mater Private Network, Dublin D07 YH66, Ireland
- School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin D02 YN77, Ireland
| | - Jens Klotsche
- German Rheumatism Research Centre Berlin, and Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medicine Berlin, Charité Mitte, Berlin 10117, Germany
| | - Michael Joner
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
- Department of Cardiology and ISAR Research Centre, German Heart Centre, Technical University Munich, Munich 80636, Germany
| | - Ulf Landmesser
- Department of Cardiology, University Heart Centre Berlin and Charité University Medicine Berlin, Campus Benjamin-Franklin (CBF), Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
- Berlin Institute of Health (BIH), 10117 Berlin, Germany
| | - David M Leistner
- Department of Cardiology, University Heart Centre Berlin and Charité University Medicine Berlin, Campus Benjamin-Franklin (CBF), Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany
- Berlin Institute of Health (BIH), 10117 Berlin, Germany
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28
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Shin J, Hong J, Edwards-Glenn J, Krukovets I, Tkachenko S, Adelus ML, Romanoski CE, Rajagopalan S, Podrez E, Byzova TV, Stenina-Adongravi O, Cherepanova OA. Unraveling the Role of Sex in Endothelial Cell Dysfunction: Evidence From Lineage Tracing Mice and Cultured Cells. Arterioscler Thromb Vasc Biol 2024; 44:238-253. [PMID: 38031841 PMCID: PMC10842863 DOI: 10.1161/atvbaha.123.319833] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 11/14/2023] [Indexed: 12/01/2023]
Abstract
BACKGROUND Biological sex differences play a vital role in cardiovascular diseases, including atherosclerosis. The endothelium is a critical contributor to cardiovascular pathologies since endothelial cells (ECs) regulate vascular tone, redox balance, and inflammatory reactions. Although EC activation and dysfunction play an essential role in the early and late stages of atherosclerosis development, little is known about sex-dependent differences in EC. METHODS We used human and mouse aortic EC as well as EC-lineage tracing (Cdh5-CreERT2 Rosa-YFP [yellow fluorescence protein]) atherosclerotic Apoe-/- mice to investigate the biological sexual dimorphism of the EC functions in vitro and in vivo. Bioinformatics analyses were performed on male and female mouse aortic EC and human lung and aortic EC. RESULTS In vitro, female human and mouse aortic ECs showed more apoptosis and higher cellular reactive oxygen species levels than male EC. In addition, female mouse aortic EC had lower mitochondrial membrane potential (ΔΨm), lower TFAM (mitochondrial transcription factor A) levels, and decreased angiogenic potential (tube formation, cell viability, and proliferation) compared with male mouse aortic EC. In vivo, female mice had significantly higher lipid accumulation within the aortas, impaired glucose tolerance, and lower endothelial-mediated vasorelaxation than males. Using the EC-lineage tracing approach, we found that female lesions had significantly lower rates of intraplaque neovascularization and endothelial-to-mesenchymal transition within advanced atherosclerotic lesions but higher incidents of missing EC lumen coverage and higher levels of oxidative products and apoptosis. RNA-seq analyses revealed that both mouse and human female EC had higher expression of genes associated with inflammation and apoptosis and lower expression of genes related to angiogenesis and oxidative phosphorylation than male EC. CONCLUSIONS Our study delineates critical sex-specific differences in EC relevant to proinflammatory, pro-oxidant, and angiogenic characteristics, which are entirely consistent with a vulnerable phenotype in females. Our results provide a biological basis for sex-specific proatherosclerotic mechanisms.
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Affiliation(s)
- Junchul Shin
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Junyoung Hong
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Jonnelle Edwards-Glenn
- Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - Irene Krukovets
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Svyatoslav Tkachenko
- Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA
| | - Maria L. Adelus
- Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ, USA
- Clinical Translational Sciences Graduate Program, The University of Arizona, Tucson, AZ, USA
| | - Casey E. Romanoski
- Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ, USA
| | - Sanjay Rajagopalan
- Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - Eugene Podrez
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Tatiana V. Byzova
- Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Olga Stenina-Adongravi
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Olga A. Cherepanova
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
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29
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Baaten CCFMJ, Nagy M, Bergmeier W, Spronk HMH, van der Meijden PEJ. Platelet biology and function: plaque erosion vs. rupture. Eur Heart J 2024; 45:18-31. [PMID: 37940193 PMCID: PMC10757869 DOI: 10.1093/eurheartj/ehad720] [Citation(s) in RCA: 37] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 07/20/2023] [Accepted: 10/11/2023] [Indexed: 11/10/2023] Open
Abstract
The leading cause of heart disease in developed countries is coronary atherosclerosis, which is not simply a result of ageing but a chronic inflammatory process that can lead to acute clinical events upon atherosclerotic plaque rupture or erosion and arterial thrombus formation. The composition and location of atherosclerotic plaques determine the phenotype of the lesion and whether it is more likely to rupture or to erode. Although plaque rupture and erosion both initiate platelet activation on the exposed vascular surface, the contribution of platelets to thrombus formation differs between the two phenotypes. In this review, plaque phenotype is discussed in relation to thrombus composition, and an overview of important mediators (haemodynamics, matrix components, and soluble factors) in plaque-induced platelet activation is given. As thrombus formation on disrupted plaques does not necessarily result in complete vessel occlusion, plaque healing can occur. Therefore, the latest findings on plaque healing and the potential role of platelets in this process are summarized. Finally, the clinical need for more effective antithrombotic agents is highlighted.
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Affiliation(s)
- Constance C F M J Baaten
- Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, the Netherlands
- Institute for Molecular Cardiovascular Research (IMCAR), University Hospital RWTH Aachen, Aachen, Germany
| | - Magdolna Nagy
- Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, the Netherlands
| | - Wolfgang Bergmeier
- Department of Biochemistry and Biophysics, School of Medicine, University of North Caroline at Chapel Hill, Chapel Hill, NC, USA
- Blood Research Center, School of Medicine, University of North Caroline at Chapel Hill, Chapel Hill, NC, USA
| | - Henri M H Spronk
- Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, the Netherlands
- Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands
- Thrombosis Expertise Center, Heart+ Vascular Center, Maastricht University Medical Center+, P. Debeyelaan 25, Maastricht, the Netherlands
| | - Paola E J van der Meijden
- Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, the Netherlands
- Thrombosis Expertise Center, Heart+ Vascular Center, Maastricht University Medical Center+, P. Debeyelaan 25, Maastricht, the Netherlands
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30
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Konishi T, Virmani R, Jinnouchi H, Kawai K, Sekimoto T, Kawakami R, Finn AV. Plaque histological characteristics in individuals with sudden coronary death. Vascul Pharmacol 2023; 153:107240. [PMID: 37898379 DOI: 10.1016/j.vph.2023.107240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 10/17/2023] [Accepted: 10/25/2023] [Indexed: 10/30/2023]
Abstract
Coronary artery disease (CAD) remains the leading cause of death in the Western world in individuals >20 years of age. CAD is the most common substrate underlying sudden cardiac death (SCD) in the Western world, being responsible for 50-75% of SCDs. In individuals dying suddenly with coronary thrombosis, plaque rupture occurs in 65%, plaque erosion in 30% and calcified nodule in 5%. We evaluated the extent of calcification in radiographs of hearts from patients dying of SCD and showed that calcification is absent in nearly 50% of erosion cases whereas only 10% of plaque rupture show no calcification. Conversely, stable plaques with >75% cross-sectional area luminal narrowing show the severest calcification (moderate to severe) in nearly 50% of cases. Identifying individuals who are susceptible to atherosclerosis may help reduce the incidence of SCD. The identification of coronary calcifications by noninvasive tools, however, only captures a fraction of complicating coronary lesions.
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Affiliation(s)
- Takao Konishi
- CVPath Institute Inc., Gaithersburg, MD, United States of America
| | - Renu Virmani
- CVPath Institute Inc., Gaithersburg, MD, United States of America.
| | | | - Kenji Kawai
- CVPath Institute Inc., Gaithersburg, MD, United States of America
| | - Teruo Sekimoto
- CVPath Institute Inc., Gaithersburg, MD, United States of America
| | - Rika Kawakami
- CVPath Institute Inc., Gaithersburg, MD, United States of America
| | - Aloke V Finn
- CVPath Institute Inc., Gaithersburg, MD, United States of America; University of Maryland, Baltimore, MD, United States of America
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31
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Noothi SK, Ahmed MR, Agrawal DK. Residual risks and evolving atherosclerotic plaques. Mol Cell Biochem 2023; 478:2629-2643. [PMID: 36897542 PMCID: PMC10627922 DOI: 10.1007/s11010-023-04689-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 02/23/2023] [Indexed: 03/11/2023]
Abstract
Atherosclerotic disease of the coronary and carotid arteries is the primary global cause of significant mortality and morbidity. The chronic occlusive diseases have changed the epidemiological landscape of health problems both in developed and the developing countries. Despite the enormous benefit of advanced revascularization techniques, use of statins, and successful attempts of targeting modifiable risk factors, like smoking and exercise in the last four decades, there is still a definite "residual risk" in the population, as evidenced by many prevalent and new cases every year. Here, we highlight the burden of the atherosclerotic diseases and provide substantial clinical evidence of the residual risks in these diseases despite advanced management settings, with emphasis on strokes and cardiovascular risks. We critically discussed the concepts and potential underlying mechanisms of the evolving atherosclerotic plaques in the coronary and carotid arteries. This has changed our understanding of the plaque biology, the progression of unstable vs stable plaques, and the evolution of plaque prior to the occurrence of a major adverse atherothrombotic event. This has been facilitated using intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy in the clinical settings to achieve surrogate end points. These techniques are now providing exquisite information on plaque size, composition, lipid volume, fibrous cap thickness and other features that were previously not possible with conventional angiography.
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Affiliation(s)
- Sunil K Noothi
- Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, USA
| | - Mohamed Radwan Ahmed
- Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, USA
| | - Devendra K Agrawal
- Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, USA.
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32
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Gurgoglione FL, Solinas E, Pfleiderer B, Vezzani A, Niccoli G. Coronary atherosclerotic plaque phenotype and physiopathologic mechanisms: Is there an influence of sex? Insights from intracoronary imaging. Atherosclerosis 2023; 384:117273. [PMID: 37730456 DOI: 10.1016/j.atherosclerosis.2023.117273] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 06/01/2023] [Accepted: 09/01/2023] [Indexed: 09/22/2023]
Abstract
Coronary artery disease (CAD) is the leading cause of disability and death in both women and men; considerable differences in clinical presentation, natural history and prognosis are reported between sexes. Different pathophysiological mechanisms play a major role, including sex-related and gender-related features or a combination of both. Reports from intracoronary imaging studies pointed towards morphological plaque features, which seemed to differ between men and women, albeit results reported so far were not conclusive. The purpose of this review is to shed light on differences in the pathophysiology underlying CAD in women vs men including the description of coronary plaque phenotype and mechanisms of plaque instability, as assessed by intracoronary imaging. We will also discuss potential clinical implications with the aim to move towards a sex and gender-based personalized approach in CAD patients.
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Affiliation(s)
| | - Emilia Solinas
- Division of Cardiology, Parma University Hospital, Parma, Italy
| | | | - Antonella Vezzani
- Cardiac Surgery Intensive Care Unit, Parma University Hospital, Parma, Italy
| | - Giampaolo Niccoli
- Division of Cardiology, University of Parma, Parma University Hospital, Parma, Italy.
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33
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Ambrose JA, Sharma AV. Identifying and Treating Vulnerable Atherosclerotic Plaques. Am J Cardiol 2023; 205:214-222. [PMID: 37611413 DOI: 10.1016/j.amjcard.2023.07.121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 07/15/2023] [Accepted: 07/24/2023] [Indexed: 08/25/2023]
Abstract
Acute coronary syndromes and, in particular, ST-elevation myocardial infarction are usually caused by coronary thrombosis in which the thrombus develops either on a disrupted plaque (usually a thin-capped fibroatheroma) or an eroded atherosclerotic plaque. These thrombus-prone plaques are vulnerable or high-risk. Although, traditionally, cardiologists have concentrated on treating significant coronary obstruction, there has been great interest over the last 2 decades in possibly preventing the thrombotic causes of myocardial infarction/sudden coronary death by mostly identifying and stabilizing these asymptomatic vulnerable or high-risk plaques, which, at least on invasive angiography, are mostly nonobstructive. Computed tomographic angiography and intravascular imaging during invasive coronary angiography have now been shown to identify a majority of these vulnerable or high-risk plaques before symptoms, thus opening up new preventive strategies. In conclusion, this article discusses the identification and management of these thrombus-prone lesions and patients with these lesions either with noninvasive techniques and systemic therapies or possibly through a new and bold interventional paradigm.
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Affiliation(s)
- John A Ambrose
- Division of Cardiology, Department of Medicine, UCSF Fresno Medical Education Program, Fresno, California.
| | - Avinash V Sharma
- Division of Cardiology, Department of Medicine, UCSF Fresno Medical Education Program, Fresno, California
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34
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Gerhardt T, Seppelt C, Abdelwahed YS, Meteva D, Wolfram C, Stapmanns P, Erbay A, Zanders L, Nelles G, Musfeld J, Sieronski L, Stähli BE, Montone RA, Vergallo R, Haghikia A, Skurk C, Knebel F, Dreger H, Trippel TD, Rai H, Joner M, Klotsche J, Libby P, Crea F, Kränkel N, Landmesser U, Leistner DM. Culprit plaque morphology determines inflammatory risk and clinical outcomes in acute coronary syndrome. Eur Heart J 2023; 44:3911-3925. [PMID: 37381774 DOI: 10.1093/eurheartj/ehad334] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 04/25/2023] [Accepted: 05/15/2023] [Indexed: 06/30/2023] Open
Abstract
AIMS Rupture of the fibrous cap (RFC) and erosion of an intact fibrous cap (IFC) are the two predominant mechanisms causing acute coronary syndromes (ACS). It is uncertain whether clinical outcomes are different following RFC-ACS vs. IFC-ACS and whether this is affected by a specific inflammatory response. The prospective, translational OPTIcal-COherence Tomography in Acute Coronary Syndrome study programme investigates the impact of the culprit lesion phenotype on inflammatory profiles and prognosis in ACS patients. METHODS AND RESULTS This analysis included 398 consecutive ACS patients, of which 62% had RFC-ACS and 25% had IFC-ACS. The primary endpoint was a composite of cardiac death, recurrent ACS, hospitalization for unstable angina, and target vessel revascularization at 2 years [major adverse cardiovascular events (MACE+)]. Inflammatory profiling was performed at baseline and after 90 days. Patients with IFC-ACS had lower rates of MACE+ than those with RFC-ACS (14.3% vs. 26.7%, P = 0.02). In 368-plex proteomic analyses, patients with IFC-ACS showed lower inflammatory proteome expression compared with those with RFC-ACS, including interleukin-6 and proteins associated with the response to interleukin-1β. Circulating plasma levels of interleukin-1β decreased from baseline to 3 months following IFC-ACS (P < 0.001) but remained stable following RFC-ACS (P = 0.25). Interleukin-6 levels decreased in patients with RFC-ACS free of MACE+ (P = 0.01) but persisted high in those with MACE+. CONCLUSION This study demonstrates a distinct inflammatory response and a lower risk of MACE+ following IFC-ACS. These findings advance our understanding of inflammatory cascades associated with different mechanisms of plaque disruption and provide hypothesis generating data for personalized anti-inflammatory therapeutic allocation to ACS patients, a strategy that merits evaluation in future clinical trials.
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Affiliation(s)
- Teresa Gerhardt
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
- Cardiovascular Research Institute and the Department of Medicine, Cardiology, Icahn School of Medicine at Mount Sinai, USA
| | - Claudio Seppelt
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
- Department of Medicine, Cardiology/Angiology, Goethe University Hospital, Frankfurt, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Frankfurt Rhine-Main, Frankfurt, Germany
| | - Youssef S Abdelwahed
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
| | - Denitsa Meteva
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
| | - Christopher Wolfram
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
| | - Philip Stapmanns
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
| | - Aslihan Erbay
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
- Department of Medicine, Cardiology/Angiology, Goethe University Hospital, Frankfurt, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Frankfurt Rhine-Main, Frankfurt, Germany
| | - Lukas Zanders
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
| | - Gregor Nelles
- Department of Medicine, Cardiology/Angiology, Goethe University Hospital, Frankfurt, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Frankfurt Rhine-Main, Frankfurt, Germany
| | - Johanna Musfeld
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
| | - Lara Sieronski
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
| | - Barbara E Stähli
- Klinik für Kardiologie, Universitäres Herzzentrum, Universitätsspital Zürich, Zurich, Switzerland
| | - Rocco A Montone
- Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Rocco Vergallo
- Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Arash Haghikia
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
| | - Carsten Skurk
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
| | - Fabian Knebel
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
- Department of Cardiology, Charité University Medicine Berlin, Campus Charité Mitte (CCM), Berlin 10117, Germany
- Sana Klinikum Lichtenberg, Innere Medizin II: Schwerpunkt Kardiologie, Berlin, Germany
| | - Henryk Dreger
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
- Department of Cardiology, Charité University Medicine Berlin, Campus Charité Mitte (CCM), Berlin 10117, Germany
| | - Tobias D Trippel
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
- Department of Cardiology, Charité University Medicine Berlin, Campus Virchow Clinic (CVK), Berlin 13353, Germany
| | - Himanshu Rai
- Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München, Technische Universität München, 80636 Munich, Germany
- Cardiovascular Research Institute (CVRI) Dublin, Mater Private Network, Dublin, Ireland
- School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland
| | - Michael Joner
- Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München, Technische Universität München, 80636 Munich, Germany
- DZHK (German Centre for Cardiovascular Research) partner Site Munich, Munich 80636, Germany
| | - Jens Klotsche
- German Rheumatism Research Center Berlin, and Institute for Social Medicine, Epidemiology und Health Economy, Charité University Medicine Berlin, Campus Charité Mitte, Berlin 10117, Germany
| | - Peter Libby
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Filippo Crea
- Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Nicolle Kränkel
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
| | - Ulf Landmesser
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
| | - David M Leistner
- Department of Cardiology, Angiology and Intensive Care Medicine CBF, Deutsches Herzzentrum der Charité, Germany and Berlin Institute of Health (BIH), Hindenburgdamm 30, Berlin 12203, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
- Department of Medicine, Cardiology/Angiology, Goethe University Hospital, Frankfurt, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Frankfurt Rhine-Main, Frankfurt, Germany
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35
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Diez Benavente E, Karnewar S, Buono M, Mili E, Hartman RJ, Kapteijn D, Slenders L, Daniels M, Aherrahrou R, Reinberger T, Mol BM, de Borst GJ, de Kleijn DP, Prange KH, Depuydt MA, de Winther MP, Kuiper J, Björkegren JL, Erdmann J, Civelek M, Mokry M, Owens GK, Pasterkamp G, den Ruijter HM. Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques. Arterioscler Thromb Vasc Biol 2023; 43:1836-1850. [PMID: 37589136 PMCID: PMC10521798 DOI: 10.1161/atvbaha.123.319325] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 07/10/2023] [Indexed: 08/18/2023]
Abstract
BACKGROUND Women presenting with coronary artery disease more often present with fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically modulated SMCs shape female versus male plaques is unknown. METHODS Gene regulatory networks were created using RNAseq gene expression data from human carotid atherosclerotic plaques. The networks were prioritized based on sex bias, relevance for smooth muscle biology, and coronary artery disease genetic enrichment. Network expression was linked to histologically determined plaque phenotypes. In addition, their expression in plaque cell types was studied at single-cell resolution using single-cell RNAseq. Finally, their relevance for disease progression was studied in female and male Apoe-/- mice fed a Western diet for 18 and 30 weeks. RESULTS Here, we identify multiple sex-stratified gene regulatory networks from human carotid atherosclerotic plaques. Prioritization of the female networks identified 2 main SMC gene regulatory networks in late-stage atherosclerosis. Single-cell RNA sequencing mapped these female networks to 2 SMC phenotypes: a phenotypically modulated myofibroblast-like SMC network and a contractile SMC network. The myofibroblast-like network was mostly expressed in plaques that were vulnerable in women. Finally, the mice ortholog of key driver gene MFGE8 (milk fat globule EGF and factor V/VIII domain containing) showed retained expression in advanced plaques from female mice but was downregulated in male mice during atherosclerosis progression. CONCLUSIONS Female atherosclerosis is characterized by gene regulatory networks that are active in fibrous vulnerable plaques rich in myofibroblast-like SMCs.
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Affiliation(s)
- Ernest Diez Benavente
- Laboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands
| | - Santosh Karnewar
- Robert M. Berne Cardiovascular Research Center (S.K., G.K.O.), University of Virginia, Charlottesville
| | - Michele Buono
- Laboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands
| | - Eloi Mili
- Laboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands
| | - Robin J.G. Hartman
- Laboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands
| | - Daniek Kapteijn
- Laboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands
| | - Lotte Slenders
- Central Diagnostic Laboratory (L.S., M.M., G.P.), University Medical Centre Utrecht, Utrecht University, the Netherlands
| | - Mark Daniels
- Laboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands
| | - Redouane Aherrahrou
- Center for Public Health Genomics (R.A., M.C.), University of Virginia, Charlottesville
- Institute for Cardiogenetics, University of Lübeck, Germany (R.A., T.R., J.E.)
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland (R.A.)
| | - Tobias Reinberger
- Institute for Cardiogenetics, University of Lübeck, Germany (R.A., T.R., J.E.)
| | - Barend M. Mol
- Department of Vascular Surgery (B.M.M., G.J.d.B., D.P.V.d.K.), University Medical Centre Utrecht, Utrecht University, the Netherlands
| | - Gert J. de Borst
- Department of Vascular Surgery (B.M.M., G.J.d.B., D.P.V.d.K.), University Medical Centre Utrecht, Utrecht University, the Netherlands
| | - Dominique P.V. de Kleijn
- Department of Vascular Surgery (B.M.M., G.J.d.B., D.P.V.d.K.), University Medical Centre Utrecht, Utrecht University, the Netherlands
| | - Koen H.M. Prange
- Experimental Vascular Biology, Department of Medical Biochemistry, Amsterdam University Medical Centers — location AMC, University of Amsterdam, Netherlands (K.H.M.P., M.P.J.d.W.)
| | - Marie A.C. Depuydt
- Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.A.C.D., J.K.)
| | - Menno P.J. de Winther
- Experimental Vascular Biology, Department of Medical Biochemistry, Amsterdam University Medical Centers — location AMC, University of Amsterdam, Netherlands (K.H.M.P., M.P.J.d.W.)
| | - Johan Kuiper
- Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.A.C.D., J.K.)
| | - Johan L.M. Björkegren
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York (J.L.M.B.)
- Department of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden (J.L.M.B.)
| | - Jeanette Erdmann
- Institute for Cardiogenetics, University of Lübeck, Germany (R.A., T.R., J.E.)
| | - Mete Civelek
- Center for Public Health Genomics (R.A., M.C.), University of Virginia, Charlottesville
- Department of Biomedical Engineering (M.C.)
- University of Virginia, Charlottesville (M.C.)
| | - Michal Mokry
- Central Diagnostic Laboratory (L.S., M.M., G.P.), University Medical Centre Utrecht, Utrecht University, the Netherlands
| | - Gary K. Owens
- Robert M. Berne Cardiovascular Research Center (S.K., G.K.O.), University of Virginia, Charlottesville
| | - Gerard Pasterkamp
- Central Diagnostic Laboratory (L.S., M.M., G.P.), University Medical Centre Utrecht, Utrecht University, the Netherlands
| | - Hester M. den Ruijter
- Laboratory of Experimental Cardiology (E.D.B., M.B., E.M., R.J.G.H., D.K., M.D., H.M.d.R.), University Medical Centre Utrecht, Utrecht University, the Netherlands
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Weng Z, Zhao C, Qin Y, Liu C, Pan W, Hu S, He L, Xu Y, Zeng M, Feng X, Gao R, Yu X, Liu M, Yi B, Zhang D, Koniaeva E, Musin T, Mohammad D, Zhu B, Sun Y, Hou J, Tian J, Mintz GS, Jia H, Yu B. Peripheral atherosclerosis in acute coronary syndrome patients with plaque rupture vs plaque erosion: A prospective coronary optical coherence tomography and peripheral ultrasound study. Am Heart J 2023; 263:159-168. [PMID: 37327980 DOI: 10.1016/j.ahj.2023.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 06/07/2023] [Accepted: 06/09/2023] [Indexed: 06/18/2023]
Abstract
BACKGROUND Plaque rupture (PR) and plaque erosion (PE) are 2 distinct, different, and most common culprit lesion morphologies responsible for acute coronary syndrome (ACS). However, the prevalence, distribution, and characteristics of peripheral atherosclerosis in ACS patients with PR vs PE has never been studied. The aim of this study was to assess peripheral atherosclerosis burden and vulnerability evaluated by vascular ultrasound in ACS patients with coronary PR vs PE identified by optical coherence tomography (OCT). METHODS Between October 2018 and December 2019, 297 ACS patients who underwent preintervention OCT examination of the culprit coronary artery were enrolled. Peripheral ultrasound examinations of carotid, femoral, and popliteal arteries were performed before discharge. RESULTS Overall, 265 of 297 (89.2%) patients had at least one atherosclerotic plaque in a peripheral arterial bed. Compared with coronary PE, patients with coronary PR had a higher prevalence of peripheral atherosclerotic plaques (93.4% vs 79.1%, P < .001), regardless of location: carotid, femoral, or popliteal arteries. The number of peripheral plaques per patient was significantly larger in the coronary PR group than coronary PE (4 [2-7] vs 2 [1-5], P < .001). Additionally, there was a greater prevalence of peripheral vulnerable characteristics including plaque surface irregularity, heterogeneous plaque, and calcification in patients with coronary PR vs PE. CONCLUSIONS Peripheral atherosclerosis exists commonly in patients presenting with ACS. Patients with coronary PR had greater peripheral atherosclerosis burden and more peripheral vulnerability compared to those with coronary PE, suggesting that comprehensive evaluation of peripheral atherosclerosis and multidisciplinary cooperative management maybe necessary, especially in patients with PR. TRIAL REGISTRATION clinicaltrials.gov (NCT03971864).
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Affiliation(s)
- Ziqian Weng
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Chen Zhao
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Yuhan Qin
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Cong Liu
- Department of Ultrasound, The second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Weili Pan
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Sining Hu
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Luping He
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Yishuo Xu
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Ming Zeng
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Xue Feng
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Rui Gao
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Xianghao Yu
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Minghao Liu
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Boling Yi
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Dirui Zhang
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Ekaterina Koniaeva
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Timur Musin
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Diler Mohammad
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Bin Zhu
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Yanli Sun
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Jingbo Hou
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Jiawei Tian
- Department of Ultrasound, The second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Gary S Mintz
- Cardiovascular Research Foundation, New York, 10019 NY, USA
| | - Haibo Jia
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
| | - Bo Yu
- Department of Cardiology, The second Affiliated Hospital of Harbin Medical University, Harbin, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China.
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Satta S, Beal R, Smith R, Luo X, Ferris GR, Langford-Smith A, Teasdale J, Ajime TT, Serré J, Hazell G, Newby GS, Johnson JL, Kurinna S, Humphries MJ, Gayan-Ramirez G, Libby P, Degens H, Yu B, Johnson T, Alexander Y, Jia H, Newby AC, White SJ. A Nrf2-OSGIN1&2-HSP70 axis mediates cigarette smoke-induced endothelial detachment: implications for plaque erosion. Cardiovasc Res 2023; 119:1869-1882. [PMID: 36804807 PMCID: PMC10405570 DOI: 10.1093/cvr/cvad022] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 12/09/2022] [Accepted: 01/05/2023] [Indexed: 02/20/2023] Open
Abstract
AIMS Endothelial erosion of plaques is responsible for ∼30% of acute coronary syndromes (ACS). Smoking is a risk factor for plaque erosion, which most frequently occurs on the upstream surface of plaques where the endothelium experiences elevated shear stress. We sought to recreate these conditions in vitro to identify potential pathological mechanisms that might be of relevance to plaque erosion. METHODS AND RESULTS Culturing human coronary artery endothelial cells (HCAECs) under elevated flow (shear stress of 7.5 Pa) and chronically exposing them to cigarette smoke extract (CSE) and tumour necrosis factor-alpha (TNFα) recapitulated a defect in HCAEC adhesion, which corresponded with augmented Nrf2-regulated gene expression. Pharmacological activation or adenoviral overexpression of Nrf2 triggered endothelial detachment, identifying Nrf2 as a mediator of endothelial detachment. Growth/Differentiation Factor-15 (GDF15) expression was elevated in this model, with protein expression elevated in the plasma of patients experiencing plaque erosion compared with plaque rupture. The expression of two Nrf2-regulated genes, OSGIN1 and OSGIN2, was increased by CSE and TNFα under elevated flow and was also elevated in the aortas of mice exposed to cigarette smoke in vivo. Knockdown of OSGIN1&2 inhibited Nrf2-induced cell detachment. Overexpression of OSGIN1&2 induced endothelial detachment and resulted in cell cycle arrest, induction of senescence, loss of focal adhesions and actin stress fibres, and disturbed proteostasis mediated in part by HSP70, restoration of which reduced HCAEC detachment. In ACS patients who smoked, blood concentrations of HSP70 were elevated in plaque erosion compared with plaque rupture. CONCLUSION We identified a novel Nrf2-OSGIN1&2-HSP70 axis that regulates endothelial adhesion, elevated GDF15 and HSP70 as biomarkers for plaque erosion in patients who smoke, and two therapeutic targets that offer the potential for reducing the risk of plaque erosion.
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Affiliation(s)
- Sandro Satta
- Department of Life Sciences, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester M1 5GD, UK
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
| | - Robert Beal
- Department of Life Sciences, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester M1 5GD, UK
| | - Rhys Smith
- Department of Life Sciences, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester M1 5GD, UK
| | - Xing Luo
- Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, & The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China
| | - Glenn R Ferris
- Department of Life Sciences, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester M1 5GD, UK
| | - Alex Langford-Smith
- Department of Life Sciences, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester M1 5GD, UK
| | - Jack Teasdale
- Bristol Medical School, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK
| | - Tom Tanjeko Ajime
- Laboratory of Respiratory Diseases and Thoracic Surgery, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Jef Serré
- Laboratory of Respiratory Diseases and Thoracic Surgery, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Georgina Hazell
- Bristol Medical School, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK
| | - Graciela Sala Newby
- Bristol Medical School, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK
| | - Jason L Johnson
- Bristol Medical School, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK
| | - Svitlana Kurinna
- Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine & Health, University of Manchester, Manchester M13 9PT, UK
| | - Martin J Humphries
- Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine & Health, University of Manchester, Manchester M13 9PT, UK
| | - Ghislaine Gayan-Ramirez
- Laboratory of Respiratory Diseases and Thoracic Surgery, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Peter Libby
- Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Hans Degens
- Department of Life Sciences, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester M1 5GD, UK
- Institute of Sport Science and Innovations, Lithuanian Sports University, Sporto g. 6, LT-44221 Kaunas, Lithuania
| | - Bo Yu
- Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, & The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China
| | - Thomas Johnson
- Department of Cardiology, Bristol Heart Institute, Upper Maudlin St., Bristol BS2 8HW, UK
| | - Yvonne Alexander
- Department of Life Sciences, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester M1 5GD, UK
| | - Haibo Jia
- Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, & The Key Laboratory of Medical Ischemia, Chinese Ministry of Education, Harbin 150086, China
| | - Andrew C Newby
- Bristol Medical School, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK
| | - Stephen J White
- Department of Life Sciences, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester M1 5GD, UK
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Seegers LM, DeFaria Yeh D, Yonetsu T, Sugiyama T, Minami Y, Soeda T, Araki M, Nakajima A, Yuki H, Kinoshita D, Suzuki K, Niida T, Lee H, McNulty I, Nakamura S, Kakuta T, Fuster V, Jang IK. Sex Differences in Coronary Atherosclerotic Phenotype and Healing Pattern on Optical Coherence Tomography Imaging. Circ Cardiovasc Imaging 2023; 16:e015227. [PMID: 37503629 DOI: 10.1161/circimaging.123.015227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 06/05/2023] [Indexed: 07/29/2023]
Abstract
BACKGROUND Layered plaque, a signature of previous plaque disruption, is a known predictor of rapid plaque progression. Layered plaque can be identified in vivo by optical coherence tomography. Studies have reported differences in plaque burden between women and men, but sex differences in the pattern of layered plaque are unknown. METHODS Preintervention optical coherence tomography images of 533 patients with chronic coronary syndromes were analyzed. Detailed plaque characteristics of layered and nonlayered plaques of the target lesion were compared between men and women. RESULTS The prevalence of layered plaque was similar between men (N=418) and women (N=115; 55% versus 54%; P=0.832). In men, more features of plaque vulnerability were identified in layered plaque than in nonlayered plaque: lipid plaque (87% versus 69%; P<0.001), macrophages (69% versus 56%; P=0.007), microvessels (72% versus 39%; P<0.001), and cholesterol crystals (49% versus 30%; P<0.001). No difference in plaque vulnerability between layered and nonlayered plaques was observed in women. Layered plaque in men had more features consistent with previous plaque rupture than in women: interrupted pattern (74% versus 52%; P<0.001) and a greater layer index (1198 [781-1835] versus 943 [624-1477]; P<0.001). CONCLUSIONS In men, layered plaques exhibit more features of vascular inflammation and vulnerability as well as evidence of previous plaque rupture, compared with nonlayered plaques, whereas in women, no difference was observed between layered and nonlayered plaques. Vascular inflammation (plaque rupture) may be the predominant mechanism of layered plaque in men, whereas a less inflammatory mechanism may play a key role in women. REGISTRATION URL: http://www. CLINICALTRIALS gov; Unique Identifier: NCT01110538, NCT04523194.
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Affiliation(s)
- Lena Marie Seegers
- Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (L.M.S., D.D.Y., M.A., A.N., H.Y., D.K., K.S., T.N., I.M.)
| | - Doreen DeFaria Yeh
- Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (L.M.S., D.D.Y., M.A., A.N., H.Y., D.K., K.S., T.N., I.M.)
| | - Taishi Yonetsu
- Department of Interventional Cardiology, Tokyo Medical and Dental University, Japan (T.Y.)
| | - Tomoyo Sugiyama
- Department of Cardiovascular Medicine, Tsuchiura Kyodo General Hospital, Ibaraki, Japan (T.S., T.K.)
| | - Yoshiyasu Minami
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan (Y.M.)
| | - Tsunenari Soeda
- Department of Cardiovascular Medicine, Nara Prefecture General Medical Center, Japan (T.S.)
| | - Makoto Araki
- Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (L.M.S., D.D.Y., M.A., A.N., H.Y., D.K., K.S., T.N., I.M.)
| | - Akihiro Nakajima
- Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (L.M.S., D.D.Y., M.A., A.N., H.Y., D.K., K.S., T.N., I.M.)
| | - Haruhito Yuki
- Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (L.M.S., D.D.Y., M.A., A.N., H.Y., D.K., K.S., T.N., I.M.)
| | - Daisuke Kinoshita
- Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (L.M.S., D.D.Y., M.A., A.N., H.Y., D.K., K.S., T.N., I.M.)
| | - Keishi Suzuki
- Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (L.M.S., D.D.Y., M.A., A.N., H.Y., D.K., K.S., T.N., I.M.)
| | - Takayuki Niida
- Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (L.M.S., D.D.Y., M.A., A.N., H.Y., D.K., K.S., T.N., I.M.)
| | - Hang Lee
- Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston (H.L.)
| | - Iris McNulty
- Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (L.M.S., D.D.Y., M.A., A.N., H.Y., D.K., K.S., T.N., I.M.)
| | - Sunao Nakamura
- Interventional Cardiology Unit, New Tokyo Hospital, Chiba, Japan (S.N.)
| | - Tsunekazu Kakuta
- Department of Cardiovascular Medicine, Tsuchiura Kyodo General Hospital, Ibaraki, Japan (T.S., T.K.)
| | - Valentin Fuster
- Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (V.F.)
| | - Ik-Kyung Jang
- Division of Cardiology, Kyung Hee University Hospital, Seoul, Korea (I.-K.J.)
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Drysdale A, Unsworth AJ, White SJ, Jones S. The Contribution of Vascular Proteoglycans to Atherothrombosis: Clinical Implications. Int J Mol Sci 2023; 24:11854. [PMID: 37511615 PMCID: PMC10380219 DOI: 10.3390/ijms241411854] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/20/2023] [Accepted: 07/22/2023] [Indexed: 07/30/2023] Open
Abstract
The vascular extracellular matrix (ECM) produced by endothelial and smooth muscle cells is composed of collagens and glycoproteins and plays an integral role in regulating the structure and function of the vascular wall. Alteration in the expression of these proteins is associated with endothelial dysfunction and has been implicated in the development and progression of atherosclerosis. The ECM composition of atherosclerotic plaques varies depending on plaque phenotype and vulnerability, with distinct differences observed between ruptured and erodes plaques. Moreover, the thrombi on the exposed ECM are diverse in structure and composition, suggesting that the best antithrombotic approach may differ depending on plaque phenotype. This review provides a comprehensive overview of the role of proteoglycans in atherogenesis and thrombosis. It discusses the differential expression of the proteoglycans in different plaque phenotypes and the potential impact on platelet function and thrombosis. Finally, the review highlights the importance of this concept in developing a targeted approach to antithrombotic treatments to improve clinical outcomes in cardiovascular disease.
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Affiliation(s)
- Amelia Drysdale
- Department of Life Sciences, Manchester Metropolitan University, Manchester M1 5GD, UK; (A.D.); (A.J.U.)
| | - Amanda J. Unsworth
- Department of Life Sciences, Manchester Metropolitan University, Manchester M1 5GD, UK; (A.D.); (A.J.U.)
| | - Stephen J. White
- Faculty of Medical Sciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK;
| | - Sarah Jones
- Department of Life Sciences, Manchester Metropolitan University, Manchester M1 5GD, UK; (A.D.); (A.J.U.)
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40
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Hakim D, Pinilla-Echeverri N, Coskun AU, Pu Z, Kajander OA, Rupert D, Maynard C, Cefalo N, Siasos G, Papafaklis MI, Kostas S, Michalis LK, Jolly S, Mehta SR, Sheth T, Croce K, Stone PH. The role of endothelial shear stress, shear stress gradient, and plaque topography in plaque erosion. Atherosclerosis 2023; 376:11-18. [PMID: 37257352 PMCID: PMC10937042 DOI: 10.1016/j.atherosclerosis.2023.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 05/12/2023] [Accepted: 05/16/2023] [Indexed: 06/02/2023]
Abstract
BACKGROUND AND AIMS Plaque erosion is a common underlying cause of acute coronary syndromes. The role of endothelial shear stress (ESS) and endothelial shear stress gradient (ESSG) in plaque erosion remains unknown. We aimed to determine the role of ESS metrics and maximum plaque slope steepness in plaques with erosion versus stable plaques. METHODS This analysis included 46 patients/plaques from TOTAL and COMPLETE trials and Brigham and Women's Hospital's database who underwent angiography and OCT. Plaques were divided into those with erosion (n = 24) and matched stable coronary plaques (n = 22). Angiographic views were used to generate a 3-D arterial reconstruction, with centerlines merged from angiography and OCT pullback. Local ESS metrics were assessed by computational fluid dynamics. Among plaque erosions, the up- and down-slope (Δ lumen area/frame) was calculated for each culprit plaque. RESULTS Compared with stable plaque controls, plaques with an erosion were associated with higher max ESS (8.3 ± 4.8 vs. 5.0 ± 1.9 Pa, p = 0.02) and max ESSG any direction (9.2 ± 7.5 vs. 4.3 ± 3.11 Pa/mm, p = 0.005). Proximal erosion was associated with a steeper plaque upslope while distal erosion with a steeper plaque downslope. Max ESS and Max ESSG any direction were independent factors in the development of plaque erosion (OR 1.32, 95%CI 1.06-1.65, p = 0.014; OR 1.22, 95% CI 1.03-1.45, p = 0.009, respectively). CONCLUSIONS In plaques with similar luminal stenosis, plaque erosion was strongly associated with higher ESS, ESS gradients, and plaque slope as compared with stable plaques. These data support that ESS and slope metrics play a key role in the development of plaque erosion and may help prognosticate individual plaques at risk for future erosion.
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Affiliation(s)
- Diaa Hakim
- Cardiovascular Division, Brigham & Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Natalia Pinilla-Echeverri
- McMaster University and Population Health Research Institute, Hamilton Health Sciences, Hamilton, Canada
| | - Ahmet U Coskun
- Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA
| | - Zhongyue Pu
- Department of Medical Science, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Olli A Kajander
- Heart Hospital, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland
| | - Deborah Rupert
- Medical Scientist Training Program, Stonybrook University, New York, NY, USA
| | - Charles Maynard
- Department of Health Systems and Population Health, University of Washington, Seattle, WA, USA
| | - Nicholas Cefalo
- Cardiovascular Division, Brigham & Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Gerasimos Siasos
- National and Kapodistrian University of Athens, Medical School, Athens, Greece
| | | | - Stefanu Kostas
- Cardiology Department, University of Ioannina, Ioannina, Greece
| | | | - Sanjit Jolly
- McMaster University and Population Health Research Institute, Hamilton Health Sciences, Hamilton, Canada
| | - Shamir R Mehta
- McMaster University and Population Health Research Institute, Hamilton Health Sciences, Hamilton, Canada
| | - Tej Sheth
- McMaster University and Population Health Research Institute, Hamilton Health Sciences, Hamilton, Canada
| | - Kevin Croce
- Cardiovascular Division, Brigham & Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Peter H Stone
- Cardiovascular Division, Brigham & Women's Hospital/Harvard Medical School, Boston, MA, USA.
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Groner J, Tognazzi M, Walter M, Fleischmann D, Mietzner R, Ziegler CE, Goepferich AM, Breunig M. Encapsulation of Pioglitazone into Polymer-Nanoparticles for Potential Treatment of Atherosclerotic Diseases. ACS APPLIED BIO MATERIALS 2023. [PMID: 37145591 DOI: 10.1021/acsabm.2c01001] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
Atherosclerosis is one of the most urgent global health subjects, causes millions of deaths worldwide, and is associated with enormous healthcare costs. Macrophages are the root cause for inflammatory onset and progression of the disease but are not addressed by conventional therapy. Therefore, we used pioglitazone, which is a drug initially used for diabetes therapies, but at the same time has great potential regarding the mitigation of inflammation. As yet, this potential of pioglitazone cannot be exploited, as drug concentrations at the target site in vivo are not sufficient. To overcome this shortcoming, we established PEG-PLA/PLGA-based nanoparticles loaded with pioglitazone and tested them in vitro. Encapsulation of the drug was analyzed by HPLC and revealed an outstanding encapsulation efficiency of 59% into the nanoparticles, which were 85 nm in size and had a PDI of 0.17. Further, uptake of our loaded nanoparticles in THP-1 macrophages was comparable to the uptake of unloaded nanoparticles. On the mRNA level, pioglitazone-loaded nanoparticles were superior to the free drug by 32% in increasing the expression of the targeted receptor PPAR-γ. Thereby the inflammatory response in macrophages was ameliorated. In this study, we take the first step toward an anti-inflammatory, causal antiatherosclerotic therapy, using the potential of the already established drug pioglitazone, and enable it to enrich at the target site by using nanoparticles. An additional crucial feature of our nanoparticle platform is the versatile modifiability of ligands and ligand density, to achieve an optimal active targeting effect in the future.
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Affiliation(s)
- Jonas Groner
- Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93053 Regensburg, Germany
| | - Martina Tognazzi
- Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93053 Regensburg, Germany
- University of Parma, Via Università 12, 43121 Parma, Italy
| | - Melanie Walter
- Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93053 Regensburg, Germany
| | - Daniel Fleischmann
- Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93053 Regensburg, Germany
| | - Raphael Mietzner
- Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93053 Regensburg, Germany
| | - Christian E Ziegler
- Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93053 Regensburg, Germany
| | - Achim M Goepferich
- Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93053 Regensburg, Germany
| | - Miriam Breunig
- Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93053 Regensburg, Germany
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42
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Cimmino G, Muscoli S, De Rosa S, Cesaro A, Perrone MA, Selvaggio S, Selvaggio G, Aimo A, Pedrinelli R, Mercuro G, Romeo F, Perrone Filardi P, Indolfi C, Coronelli M. Evolving concepts in the pathophysiology of atherosclerosis: from endothelial dysfunction to thrombus formation through multiple shades of inflammation. J Cardiovasc Med (Hagerstown) 2023; 24:e156-e167. [PMID: 37186566 DOI: 10.2459/jcm.0000000000001450] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
Atherosclerosis is the anatomo-pathological substrate of most cardio, cerebro and vascular diseases such as acute and chronic coronary syndromes, stroke and peripheral artery diseases. The pathophysiology of atherosclerotic plaque and its complications are under continuous investigation. In the last 2 decades our understanding on the formation, progression and complication of the atherosclerotic lesion has greatly improved and the role of immunity and inflammation is now well documented and accepted. The conventional risk factors modulate endothelial function determining the switch to a proatherosclerotic phenotype. From this point, lipid accumulation with an imbalance from cholesterol influx and efflux, foam cells formation, T-cell activation, cytokines release and matrix-degrading enzymes production occur. Lesions with high inflammatory rate become vulnerable and prone to rupture. Once complicated, the intraplaque thrombogenic material, such as the tissue factor, is exposed to the flowing blood, thus inducing coagulation cascade activation, platelets aggregation and finally intravascular thrombus formation that leads to clinical manifestations of this disease. Nonconventional risk factors, such as gut microbiome, are emerging novel markers of atherosclerosis. Several data indicate that gut microbiota may play a causative role in formation, progression and complication of atherosclerotic lesions. The gut dysbiosis-related inflammation and gut microbiota-derived metabolites have been proposed as the main working hypothesis in contributing to disease formation and progression. The current evidence suggest that the conventional and nonconventional risk factors may modulate the degree of inflammation of the atherosclerotic lesion, thus influencing its final fate. Based on this hypothesis, targeting inflammation seems to be a promising approach to further improve our management of atherosclerotic-related diseases.
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Affiliation(s)
- Giovanni Cimmino
- Department of Translational Medical Sciences, University of Campania 'Luigi Vanvitelli', Naples
| | | | - Salvatore De Rosa
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Catanzaro
| | - Arturo Cesaro
- Department of Translational Medical Sciences, University of Campania 'Luigi Vanvitelli', Naples
- Division of Cardiology, A.O.R.N. 'Sant'Anna e San Sebastiano', Caserta
| | - Marco A Perrone
- Department of Cardiology and CardioLab, University of Rome Tor Vergata, Rome
| | | | | | - Alberto Aimo
- Fondazione Toscana Gabriele Monasterio
- Institute of Life Sciences, Scuola Superiore Sant'Anna
| | - Roberto Pedrinelli
- Critical Care Medicine-Cardiology Division, Department of Surgical, Medical and Molecular Pathology, University of Pisa, Pisa
| | - Giuseppe Mercuro
- Dipartimento di Scienze Mediche e Sanità Pubblica, Università degli Studi, Cagliari
| | | | - Pasquale Perrone Filardi
- Dipartimento di Scienze Biomediche Avanzate, Università degli Studi di Napoli 'Federico II', Napoli
| | - Ciro Indolfi
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Catanzaro
| | - Maurizio Coronelli
- Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy
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43
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Nishimiya K, Poduval RK, Tearney GJ. OCT Emerging Technologies: Coronary Micro-optical Coherence Tomography. Interv Cardiol Clin 2023; 12:237-244. [PMID: 36922064 DOI: 10.1016/j.iccl.2023.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/14/2023]
Abstract
Optical coherence tomography (OCT) is an imaging modality that is used in a significant number of interventional cardiology procedures. Key structural changes occurring within the vessel wall, including presence of neutrophils, macrophages, monocytes, and vascular smooth muscle cells, are below the resolution of clinical intracoronary OCT. To address this challenge, a new form of OCT with 1 to 2 μm resolution, termed micro-OCT (μOCT), has been developed. This review article summarizes the ability of μOCT technology to visualize coronary microstructures and discusses its clinical implications.
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Affiliation(s)
- Kensuke Nishimiya
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
| | - Radhika K Poduval
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Guillermo J Tearney
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; Harvard-MIT Division of Health Sciences and Technology Division, Cambridge, MA, USA.
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44
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An automatic entropy method to efficiently mask histology whole-slide images. Sci Rep 2023; 13:4321. [PMID: 36922520 PMCID: PMC10017682 DOI: 10.1038/s41598-023-29638-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 02/08/2023] [Indexed: 03/18/2023] Open
Abstract
Tissue segmentation of histology whole-slide images (WSI) remains a critical task in automated digital pathology workflows for both accurate disease diagnosis and deep phenotyping for research purposes. This is especially challenging when the tissue structure of biospecimens is relatively porous and heterogeneous, such as for atherosclerotic plaques. In this study, we developed a unique approach called 'EntropyMasker' based on image entropy to tackle the fore- and background segmentation (masking) task in histology WSI. We evaluated our method on 97 high-resolution WSI of human carotid atherosclerotic plaques in the Athero-Express Biobank Study, constituting hematoxylin and eosin and 8 other staining types. Using multiple benchmarking metrics, we compared our method with four widely used segmentation methods: Otsu's method, Adaptive mean, Adaptive Gaussian and slideMask and observed that our method had the highest sensitivity and Jaccard similarity index. We envision EntropyMasker to fill an important gap in WSI preprocessing, machine learning image analysis pipelines, and enable disease phenotyping beyond the field of atherosclerosis.
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45
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Emfietzoglou M, Mavrogiannis MC, García-García HM, Stamatelopoulos K, Kanakakis I, Papafaklis MI. Current Toolset in Predicting Acute Coronary Thrombotic Events: The "Vulnerable Plaque" in a "Vulnerable Patient" Concept. Life (Basel) 2023; 13:696. [PMID: 36983851 PMCID: PMC10052113 DOI: 10.3390/life13030696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 03/01/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023] Open
Abstract
Despite major advances in pharmacotherapy and interventional procedures, coronary artery disease (CAD) remains a principal cause of morbidity and mortality worldwide. Invasive coronary imaging along with the computation of hemodynamic forces, primarily endothelial shear stress and plaque structural stress, have enabled a comprehensive identification of atherosclerotic plaque components, providing a unique insight into the understanding of plaque vulnerability and progression, which may help guide patient treatment. However, the invasive-only approach to CAD has failed to show high predictive value. Meanwhile, it is becoming increasingly evident that along with the "vulnerable plaque", the presence of a "vulnerable patient" state is also necessary to precipitate an acute coronary thrombotic event. Non-invasive imaging techniques have also evolved, providing new opportunities for the identification of high-risk plaques, the study of atherosclerosis in asymptomatic individuals, and general population screening. Additionally, risk stratification scores, circulating biomarkers, immunology, and genetics also complete the armamentarium of a broader "vulnerable plaque and patient" concept approach. In the current review article, the invasive and non-invasive modalities used for the detection of high-risk plaques in patients with CAD are summarized and critically appraised. The challenges of the vulnerable plaque concept are also discussed, highlighting the need to shift towards a more interdisciplinary approach that can identify the "vulnerable plaque" in a "vulnerable patient".
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Affiliation(s)
| | - Michail C. Mavrogiannis
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK
| | - Hector M. García-García
- Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC 20010, USA
| | - Kimon Stamatelopoulos
- Department of Therapeutics, Faculty of Medicine, National and Kapodistrian University of Athens, 157 72 Athens, Greece
| | - Ioannis Kanakakis
- Catheterization and Hemodynamic Unit, Alexandra University Hospital, 115 28 Athens, Greece
| | - Michail I. Papafaklis
- Catheterization and Hemodynamic Unit, Alexandra University Hospital, 115 28 Athens, Greece
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46
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A Comprehensive Review: Epidemiological strategies, Catheterization and Biomarkers used as a Bioweapon in Diagnosis and Management of Cardio Vascular Diseases. Curr Probl Cardiol 2023; 48:101661. [PMID: 36822564 DOI: 10.1016/j.cpcardiol.2023.101661] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 02/17/2023] [Indexed: 02/23/2023]
Abstract
Coronary artery disease (CAD) is a serious health problem that causes a considerable number of mortality in a number of affluent nations throughout the world. The estimated death encountered in many developed countries includes including Pakistan, reached 111,367 and accounted for 9.87% of all deaths, despite the mortality rate being around 7.2 million deaths per year, or 12% of all estimated deaths accounted annually around the globe, with improved health systems. Atherosclerosis progressing causes the coronary arteries to become partially or completely blocked, which results in CAD. Additionally, smoking, diabetes mellitus, homocystinuria, hypertension, obesity, hyperlipidemia, and psychological stress are risk factors for CAD. The symptoms of CAD include angina which is described as a burning, pain or discomfort in the chest, nausea, weakness, shortness of breath, lightheadedness, and pain or discomfort in the arms or shoulders. Atherosclerosis and thrombosis are the two pathophysiological pathways most frequently involved in acute coronary syndrome (ACS). Asymptomatic plaque disruption, plaque bleeding, symptomatic coronary blockage, and myocardial infarction are the prognoses for CAD. In this review, we will focus on medicated therapy which is being employed for the relief of angina linked with CAD including antiplatelet medicines, nitrates, calcium antagonists, blockers, catheterization, and the frequency of recanalized infarct-related arteries in patients with acute anterior wall myocardial infarction (AWMI). Furthermore, we have also enlightened the importance of biomarkers that are helpful in the diagnosis and management of CAD.
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47
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Benavente ED, Karnewar S, Buono M, Mili E, Hartman RJG, Kapteijn D, Slenders L, Daniels M, Aherrahrou R, Reinberger T, Mol BM, de Borst GJ, de Kleijn DPV, Prange KHM, Depuydt MAC, de Winther MPJ, Kuiper J, Björkegren JLM, Erdmann J, Civelek M, Mokry M, Owens GK, Pasterkamp G, den Ruijter HM. Female gene networks are expressed in myofibroblast-like smooth muscle cells in vulnerable atherosclerotic plaques. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.02.08.527690. [PMID: 36798294 PMCID: PMC9934638 DOI: 10.1101/2023.02.08.527690] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Women presenting with coronary artery disease (CAD) more often present with fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically modulated SMCs shape female versus male plaques is unknown. Here, we show sex-stratified gene regulatory networks (GRNs) from human carotid atherosclerotic tissue. Prioritization of these networks identified two main SMC GRNs in late-stage atherosclerosis. Single-cell RNA-sequencing mapped these GRNs to two SMC phenotypes: a phenotypically modulated myofibroblast-like SMC network and a contractile SMC network. The myofibroblast-like GRN was mostly expressed in plaques that were vulnerable in females. Finally, mice orthologs of the female myofibroblast-like genes showed retained expression in advanced plaques from female mice but were downregulated in male mice during atherosclerosis progression. Female atherosclerosis is driven by GRNs that promote a fibrous vulnerable plaque rich in myofibroblast-like SMCs.
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Affiliation(s)
- Ernest Diez Benavente
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Santosh Karnewar
- Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA
| | - Michele Buono
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Eloi Mili
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Robin J. G. Hartman
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Daniek Kapteijn
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Lotte Slenders
- Central Diagnostic Laboratory, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Mark Daniels
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Redouane Aherrahrou
- Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
- Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
| | | | - Barend M. Mol
- Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, Utrecht University, The Netherlands
| | - Gert J. de Borst
- Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, Utrecht University, The Netherlands
| | - Dominique P. V. de Kleijn
- Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, Utrecht University, The Netherlands
| | - Koen H. M. Prange
- Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University’ Leiden, The Netherlands
| | - Marie A. C. Depuydt
- Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University’ Leiden, The Netherlands
| | - Menno P. J. de Winther
- Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University’ Leiden, The Netherlands
| | - Johan Kuiper
- Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University’ Leiden, The Netherlands
| | - Johan L. M. Björkegren
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden
| | - Jeanette Erdmann
- Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany
| | - Mete Civelek
- Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
- Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA
| | - Michal Mokry
- Central Diagnostic Laboratory, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Gary K Owens
- Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA
| | - Gerard Pasterkamp
- Central Diagnostic Laboratory, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Hester M. den Ruijter
- Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, the Netherlands
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48
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Goh WX, Kok YY, Wong CY. Comparison of Cell-based and Nanoparticle-based Therapeutics in Treating Atherosclerosis. Curr Pharm Des 2023; 29:2827-2840. [PMID: 37936453 DOI: 10.2174/0113816128272185231024115046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 09/06/2023] [Accepted: 09/14/2023] [Indexed: 11/09/2023]
Abstract
Today, cardiovascular diseases are among the biggest public health threats worldwide. Atherosclerosis, a chronic inflammatory disease with complex aetiology and pathogenesis, predispose many of these conditions, including the high mortality rate-causing ischaemic heart disease and stroke. Nevertheless, despite the alarming prevalence and absolute death rate, established treatments for atherosclerosis are unsatisfactory in terms of efficacy, safety, and patient acceptance. The rapid advancement of technologies in healthcare research has paved new treatment approaches, namely cell-based and nanoparticle-based therapies, to overcome the limitations of conventional therapeutics. This paper examines the different facets of each approach, discusses their principles, strengths, and weaknesses, analyses the main targeted pathways and their contradictions, provides insights on current trends as well as highlights any unique mechanisms taken in recent years to combat the progression of atherosclerosis.
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Affiliation(s)
- Wen Xi Goh
- Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur, Malaysia
| | - Yih Yih Kok
- Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur, Malaysia
| | - Chiew Yen Wong
- Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur, Malaysia
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49
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Biswas D, Roy S, Vasudevan S. Biomedical Application of Photoacoustics: A Plethora of Opportunities. MICROMACHINES 2022; 13:1900. [PMID: 36363921 PMCID: PMC9692656 DOI: 10.3390/mi13111900] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/19/2022] [Accepted: 10/29/2022] [Indexed: 06/16/2023]
Abstract
The photoacoustic (PA) technique is a non-invasive, non-ionizing hybrid technique that exploits laser irradiation for sample excitation and acquires an ultrasound signal generated due to thermoelastic expansion of the sample. Being a hybrid technique, PA possesses the inherent advantages of conventional optical (high resolution) and ultrasonic (high depth of penetration in biological tissue) techniques and eliminates some of the major limitations of these conventional techniques. Hence, PA has been employed for different biomedical applications. In this review, we first discuss the basic physics of PA. Then, we discuss different aspects of PA techniques, which includes PA imaging and also PA frequency spectral analysis. The theory of PA signal generation, detection and analysis is also detailed in this work. Later, we also discuss the major biomedical application area of PA technique.
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Affiliation(s)
- Deblina Biswas
- School of Bioengineering and Food Technology, Shoolini University, Solan 173229, HP, India
| | - Swarup Roy
- School of Bioengineering and Food Technology, Shoolini University, Solan 173229, HP, India
| | - Srivathsan Vasudevan
- Discipline of Electrical Engineering, Indian Institute of Technology Indore, Khandwa Road, Simrol 453552, MP, India
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50
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Phyo WSY, Shirakawa M, Yamada K, Kuwahara S, Yoshimura S. Characteristics of Calcification and Their Association with Carotid Plaque Vulnerability. World Neurosurg 2022; 167:e1017-e1024. [PMID: 36058484 DOI: 10.1016/j.wneu.2022.08.127] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Accepted: 08/28/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Carotid plaque vulnerability is one of the important features for evaluating the risk of subsequent ischemic stroke. Although magnetic resonance imaging (MRI) is the gold standard modality for evaluating plaque vulnerability, some patients cannot undergo MRI because of physical or economic issues. Computed tomography (CT) is more readily available. The purpose of this study was to establish a new category of calcification on CT and to assess its usefulness for detecting vulnerable plaque. MATERIALS AND METHODS We retrospectively evaluated consecutive patients who underwent plaque imaging using CT and MRI before carotid revascularization at our institute. Calcifications were classified into 4 types according to the new calcium classification. The patients were divided into 2 groups, the double layer sign (DLS)-positive group and the DLS-negative group. Signal intensity ratio (SIR) of carotid plaque was measured on MRI for evaluating plaque vulnerability and compared between type of calcification and SIR. RESULTS Among the 132 patients evaluated, 50 patients (62.5%) in DLS positive group and 16 patients (30.8%) in DLS negative group had calcification with vulnerable plaque (SIR > 1.47) (P < 0.01). Substantial interobserver agreement of type of calcification was observed (kappa, 0.79; P < 0.01). Multivariate analysis showed that DLS (odds ratio 3.03; 95% confidence interval 1.35-6.8; P < 0.01) and male sex (odds ratio 3.15; 95% confidence interval 1.02-9.68; P = 0.04) were independent predictors of vulnerable plaque. CONCLUSIONS DLS in our new classification of calcification on CT reliably detects vulnerable plaque and could thus be used in patients who cannot undergo MRI.
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Affiliation(s)
- Wint Shwe Yee Phyo
- Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Manabu Shirakawa
- Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Kiyofumi Yamada
- Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Shuntaro Kuwahara
- Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Shinichi Yoshimura
- Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
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