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1
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Papadopoulos KI, Papadopoulou A, Aw TC. MicroRNA-155 modulation by renin-angiotensin system inhibitors may underlie their enigmatic role in COVID-19. World J Exp Med 2025; 15:100748. [DOI: 10.5493/wjem.v15.i2.100748] [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: 08/25/2024] [Revised: 01/18/2025] [Accepted: 02/06/2025] [Indexed: 04/16/2025] Open
Abstract
Severe acute respiratory coronavirus-2 (SARS-CoV-2) infection course differs between the young and healthy and the elderly with co-morbidities. In the latter a potentially lethal coronavirus disease 2019 (COVID-19) cytokine storm has been described with an unrestrained renin-angiotensin (Ang) system (RAS). RAS inhibitors [Ang converting enzyme inhibitors and Ang II type 1 receptor (AT1R) blockers] while appearing appropriate in COVID-19, display enigmatic effects ranging from protection to harm. MicroRNA-155 (miR-155)-induced translational repression of key cardiovascular (CV) genes (i.e., AT1R) restrains SARS-CoV-2-engendered RAS hyperactivity to tolerable and SARS-CoV-2-protective CV phenotypes supporting a protective erythropoietin (EPO) evolutionary landscape. MiR-155’s disrupted repression of the AT1R 1166C-allele associates with adverse CV and COVID-19 outcomes, confirming its decisive role in RAS modulation. RAS inhibition disrupts this miR-155-EPO network by further lowering EPO and miR-155 in COVID-19 with co-morbidities, thereby allowing unimpeded RAS hyperactivity to progress precariously. Current pharmacological interventions in COVID-19 employing RAS inhibition should consider these complex but potentially detrimental miR-155/EPO-related effects.
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Affiliation(s)
| | - Alexandra Papadopoulou
- Department of Occupational and Environmental Health Services, Feelgood Lund, Lund 223-63, Skåne, Sweden
| | - Tar Choon Aw
- Department of Laboratory Medicine, Changi General Hospital, Singapore 529889, Singapore
- Department of Medicine, National University of Singapore, Singapore 119228, Singapore
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2
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Khan K, Khan A, Rahman ZU, Khan F, Latief N, Fazal N. Genetic Polymorphism in miRNA Genes and Their Association with susceptibility of Coronary Heart Disease: An Updated Review. Pathol Res Pract 2024; 264:155675. [PMID: 39488988 DOI: 10.1016/j.prp.2024.155675] [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: 07/10/2024] [Revised: 10/18/2024] [Accepted: 10/24/2024] [Indexed: 11/05/2024]
Abstract
Coronary heart disease (CHD) remains a major public health concern worldwide, with a complex interplay of genetic, environmental and lifestyle factors contributing to its pathogenesis. The potential significance of microRNAs (miRNAs) in the onset and progression of CHD has attracted increasing attention in recent years. Small non-coding RNA molecules called miRNAs control gene expression at the post-transcriptional level. Dysregulation of miRNAs has been linked to a variety of biological processes, including cell division, proliferation, apoptosis, and inflammation. Numerous research studies have looked into the relationship between genetic variants in miRNA genes and CHD susceptibility. This review highlights the recent research work carried out to identify the relationship of miRNA genes polymorphism with the progression and susceptibility of CHD. Such studies could pave the way for the development of personalized strategies for CHD prevention and treatment based on an individual's genetic profile.
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Affiliation(s)
- Khalid Khan
- National Centre of Excellence in Molecular Biology, University of the Punjab, Pakistan
| | - Aakif Khan
- National Centre of Excellence in Molecular Biology, University of the Punjab, Pakistan
| | - Zia Ur Rahman
- University Institute of Medical Laboratory Technology, the University of Lahore, Pakistan
| | - Faisal Khan
- National Centre of Excellence in Molecular Biology, University of the Punjab, Pakistan
| | - Noreen Latief
- National Centre of Excellence in Molecular Biology, University of the Punjab, Pakistan
| | - Numan Fazal
- University Institute of Medical Laboratory Technology, the University of Lahore, Pakistan.
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3
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Eshraghi R, Rafiei M, Hadian Jazi Z, Shafie D, Raisi A, Mirzaei H. MicroRNA-155 and exosomal microRNA-155: Small pieces in the cardiovascular diseases puzzle. Pathol Res Pract 2024; 257:155274. [PMID: 38626659 DOI: 10.1016/j.prp.2024.155274] [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: 02/14/2024] [Revised: 03/23/2024] [Accepted: 03/26/2024] [Indexed: 04/18/2024]
Abstract
MicroRNAs (miRs, miRNAs) are known to have a part in various human illnesses, such as those related to the heart. One particular miRNA, miR-155, has been extensively studied and has been found to be involved in hematopoietic lineage differentiation, immunity, viral infections, inflammation, as well as vascular remodeling. These processes have all been connected to cardiovascular diseases, including heart failure, diabetic heart disease, coronary artery disease, and abdominal aortic aneurysm. The impacts of miR-155 depend on the type of cell it is acting on and the specific target genes involved, resulting in different mechanisms of disease. Although, the exact part of miR-155 in cardiovascular illnesses is yet not fully comprehended, as some studies have shown it to promote the development of atherosclerosis while others have shown it to prevent it. As a result, to comprehend the underlying processes of miR-155 in cardiovascular disorders, further thorough study is required. It has been discovered that exosomes that could be absorbed by adjacent or distant cells, control post-transcriptional regulation of gene expression by focusing on mRNA. Exosomal miRNAs have been found to have a range of functions, including participating in inflammatory reactions, cell movement, growth, death, autophagy, as well as epithelial-mesenchymal transition. An increasing amount of research indicates that exosomal miRNAs are important for cardiovascular health and have a major role in the development of a number of cardiovascular disorders, including pulmonary hypertension, atherosclerosis, acute coronary syndrome, heart failure, and myocardial ischemia-reperfusion injury. Herein the role of miR-155 and its exosomal form in heart diseases are summarized.
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Affiliation(s)
- Reza Eshraghi
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran.
| | - Moein Rafiei
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Zahra Hadian Jazi
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Davood Shafie
- Cardiology/Heart Failure and Transplantation, Heart Failure Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Arash Raisi
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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4
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Wańczura P, Aebisher D, Iwański MA, Myśliwiec A, Dynarowicz K, Bartusik-Aebisher D. The Essence of Lipoproteins in Cardiovascular Health and Diseases Treated by Photodynamic Therapy. Biomedicines 2024; 12:961. [PMID: 38790923 PMCID: PMC11117957 DOI: 10.3390/biomedicines12050961] [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: 03/10/2024] [Revised: 04/22/2024] [Accepted: 04/24/2024] [Indexed: 05/26/2024] Open
Abstract
Lipids, together with lipoprotein particles, are the cause of atherosclerosis, which is a pathology of the cardiovascular system. In addition, it affects inflammatory processes and affects the vessels and heart. In pharmaceutical answer to this, statins are considered a first-stage treatment method to block cholesterol synthesis. Many times, additional drugs are also used with this method to lower lipid concentrations in order to achieve certain values of low-density lipoprotein (LDL) cholesterol. Recent advances in photodynamic therapy (PDT) as a new cancer treatment have gained the therapy much attention as a minimally invasive and highly selective method. Photodynamic therapy has been proven more effective than chemotherapy, radiotherapy, and immunotherapy alone in numerous studies. Consequently, photodynamic therapy research has expanded in many fields of medicine due to its increased therapeutic effects and reduced side effects. Currently, PDT is the most commonly used therapy for treating age-related macular degeneration, as well as inflammatory diseases, and skin infections. The effectiveness of photodynamic therapy against a number of pathogens has also been demonstrated in various studies. Also, PDT has been used in the treatment of cardiovascular diseases, such as atherosclerosis and hyperplasia of the arterial intima. This review evaluates the effectiveness and usefulness of photodynamic therapy in cardiovascular diseases. According to the analysis, photodynamic therapy is a promising approach for treating cardiovascular diseases and may lead to new clinical trials and management standards. Our review addresses the used therapeutic strategies and also describes new therapeutic strategies to reduce the cardiovascular burden that is induced by lipids.
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Affiliation(s)
- Piotr Wańczura
- Department of Cardiology, Medical College of the University of Rzeszów, 35-310 Rzeszów, Poland
| | - David Aebisher
- Department of Photomedicine and Physical Chemistry, Medical College of the University of Rzeszów, 35-310 Rzeszów, Poland
| | - Mateusz A Iwański
- English Division Science Club, Medical College of the University of Rzeszów, 35-310 Rzeszów, Poland
| | - Angelika Myśliwiec
- Center for Innovative Research in Medical and Natural Sciences, Medical College of the University of Rzeszów, 35-310 Rzeszów, Poland
| | - Klaudia Dynarowicz
- Center for Innovative Research in Medical and Natural Sciences, Medical College of the University of Rzeszów, 35-310 Rzeszów, Poland
| | - Dorota Bartusik-Aebisher
- Department of Biochemistry and General Chemistry, Medical College of the University of Rzeszów, 35-310 Rzeszów, Poland
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5
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Searles CD. MicroRNAs and Cardiovascular Disease Risk. Curr Cardiol Rep 2024; 26:51-60. [PMID: 38206553 PMCID: PMC10844442 DOI: 10.1007/s11886-023-02014-1] [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] [Accepted: 12/10/2023] [Indexed: 01/12/2024]
Abstract
PURPOSE OF REVIEW MicroRNAs (miRNAs)-short, non-coding RNAs-play important roles in almost all aspects of cardiovascular biology, and changes in intracellular miRNA expression are indicative of cardiovascular disease development and progression. Extracellular miRNAs, which are easily measured in blood and can be reflective of changes in intracellular miRNA levels, have emerged as potential non-invasive biomarkers for disease. This review summarizes current knowledge regarding miRNAs as biomarkers for assessing cardiovascular disease risk and prognosis. RECENT FINDINGS Numerous studies over the last 10-15 years have identified associations between extracellular miRNA profiles and cardiovascular disease, supporting the potential use of extracellular miRNAs as biomarkers for risk stratification. However, clinical application of extracellular miRNA profiles has been hampered by poor reproducibility and inter-study variability that is due largely to methodological differences between studies. While recent studies indicate that circulating extracellular miRNAs are promising biomarkers for cardiovascular disease, evidence for clinical implementation is lacking. This highlights the need for larger, well-designed studies that use standardized methods for sample preparation, miRNA isolation, quantification, and normalization.
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Affiliation(s)
- Charles D Searles
- Emory University School of Medicine and Atlanta VA Health Care System, 1670 Clairmont Road, Decatur, GA, 30033, USA.
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Macvanin MT, Gluvic ZM, Klisic AN, Manojlovic MS, Suri JS, Rizzo M, Isenovic ER. The Link between miRNAs and PCKS9 in Atherosclerosis. Curr Med Chem 2024; 31:6926-6956. [PMID: 37990898 DOI: 10.2174/0109298673262124231102042914] [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: 05/12/2023] [Revised: 06/30/2023] [Accepted: 09/11/2023] [Indexed: 11/23/2023]
Abstract
Cardiovascular disease (CDV) represents the major cause of death globally. Atherosclerosis, as the primary cause of CVD, is a chronic immune-inflammatory disorder with complex multifactorial pathophysiology encompassing oxidative stress, enhanced immune-inflammatory cascade, endothelial dysfunction, and thrombosis. An initiating event in atherosclerosis is the subendothelial accumulation of low-density lipoprotein (LDL), followed by the localization of macrophages to fatty deposits on blood vessel walls, forming lipid-laden macrophages (foam cells) that secrete compounds involved in plaque formation. Given the fact that foam cells are one of the key culprits that underlie the pathophysiology of atherosclerosis, special attention has been paid to the investigation of the efficient therapeutic approach to overcome the dysregulation of metabolism of cholesterol in macrophages, decrease the foam cell formation and/or to force its degradation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serine proteinase that has emerged as a significant regulator of the lipid metabolism pathway. PCSK9 activation leads to the degradation of LDL receptors (LDLRs), increasing LDL cholesterol (LDL-C) levels in the circulation. PCSK9 pathway dysregulation has been identified as one of the mechanisms involved in atherosclerosis. In addition, microRNAs (miRNAs) are investigated as important epigenetic factors in the pathophysiology of atherosclerosis and dysregulation of lipid metabolism. This review article summarizes the recent findings connecting the role of PCSK9 in atherosclerosis and the involvement of various miRNAs in regulating the expression of PCSK9-related genes. We also discuss PCSK9 pathway-targeting therapeutic interventions based on PCSK9 inhibition, and miRNA levels manipulation by therapeutic agents.
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Affiliation(s)
- Mirjana T Macvanin
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Zoran M Gluvic
- Department of Endocrinology and Diabetes, School of Medicine, University Clinical-Hospital Centre Zemun-Belgrade, Clinic of Internal Medicine, University of Belgrade, Belgrade, Serbia
| | - Aleksandra N Klisic
- Faculty of Medicine, Center for Laboratory Diagnostic, Primary Health Care Center, University of Montenegro, Podgorica, Montenegro
| | - Mia S Manojlovic
- Faculty of Medicine Novi Sad, University of Novi Sad, Novi Sad, Serbia
- Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Center of Vojvodina, Novi Sad, Serbia
| | - Jasjit S Suri
- Stroke Monitoring and Diagnostic Division, Athero- Point™, Roseville, CA95661, USA
| | - Manfredi Rizzo
- Department of Health Promotion, School of Medicine, Mother and Child Care and Medical Specialties (Promise), University of Palermo, Palermo, Italy
| | - Esma R Isenovic
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
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Saadatian Z, Mansoori Y, Nariman-Saleh-Fam L, Daraei A, Vahed SZ, Navid S, Nariman-Saleh-Fam Z. Peripheral blood mononuclear cells expression of miR-200c, miR-125b, miR-27b, miR-203, and miR-155 in patients with significant or insignificant coronary artery stenosis. Sci Rep 2023; 13:18438. [PMID: 37891322 PMCID: PMC10611722 DOI: 10.1038/s41598-023-45146-8] [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: 01/05/2023] [Accepted: 10/16/2023] [Indexed: 10/29/2023] Open
Abstract
Coronary artery disease (CAD) is one of the principal causes of death worldwide. Among several predisposing factors, inflammation and inflammatory genes play a significant role in disease pathogenesis. Inflammatory microRNAs, small noncoding RNAs involved in regulating inflammation, are promising candidates for understanding pathogenesis of CAD and developing diagnostic biomarkers. The aim of the study was to evaluate the alteration of miR-200c, miR-125b, miR-27b, miR-203 and, miR-155 in patients suffering from coronary artery stenosis and insignificant coronary artery stenosis compared to healthy subjects. In this study we compared expressions of five inflammatory miRNAs in peripheral blood mononuclear cells (PBMCs) of 72 patients suffering significant coronary artery stenosis (CAD), 74 individuals without coronary artery disease and 30 individuals with insignificant coronary artery stenosis (ICAD). After blood collection, PBMCs were isolated and RNA was extracted. Gene expression levels were assessed by SYBR green based real-time PCR. Statistical analysis was performed using R program. Expression levels of miR-200c, miR-203, and miR-155 were lower in subjects with ICAD than that in CAD patients and subjects of the control group. MiR-125b was downregulated in CAD and ICAD groups compared to the control group. PBMC miR-27b was upregulated in the CAD group as compared to the ICAD and control groups. Receiver operating characteristic curve analysis verified potential of three miRNAs in separating subjects with ICAD from CAD patients and healthy individuals. In conclusion, this original investigation suggested that altered expression of these five miRNAs may serve as a novel diagnostic biomarker discriminating clinical presentations of coronary artery diseases.
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Affiliation(s)
- Zahra Saadatian
- Department of Physiology, Faculty of Medicine, Infectious Diseases Research Center, Gonabad University of Medical Sciences, Gonabad, Iran.
| | - Yaser Mansoori
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
| | | | - Abdolreza Daraei
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | | | - Shadan Navid
- Department of Anatomy, Faculty of Medicine, Social Determinants of Health Research Center, Gonabad University of Medical Science, Gonabad, Iran
| | - Ziba Nariman-Saleh-Fam
- Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Clinical Research Development Unit, Shohada Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
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Papadopoulos KI, Papadopoulou A, Aw TC. MicroRNA-155 mediates endogenous angiotensin II type 1 receptor regulation: implications for innovative type 2 diabetes mellitus management. World J Diabetes 2023; 14:1334-1340. [PMID: 37771329 PMCID: PMC10523232 DOI: 10.4239/wjd.v14.i9.1334] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 06/18/2023] [Accepted: 07/13/2023] [Indexed: 09/13/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a lifelong condition and a threat to human health. Thorough understanding of its pathogenesis is acutely needed in order to devise innovative, preventative, and potentially curative pharmacological interventions. MicroRNAs (miRNA), are small, non-coding, one-stranded RNA molecules, that can target and silence around 60% of all human genes through translational repression. MiR-155 is an ancient, evolutionarily well-conserved miRNA, with distinct expression profiles and multifunctionality, and a target repertoire of over 241 genes involved in numerous physiological and pathological processes including hematopoietic lineage differentiation, immunity, inflammation, viral infections, cancer, cardiovascular conditions, and particularly diabetes mellitus. MiR-155 Levels are progressively reduced in aging, obesity, sarcopenia, and T2DM. Thus, the loss of coordinated repression of multiple miR-155 targets acting as negative regulators, such as C/EBPβ, HDAC4, and SOCS1 impacts insulin signaling, deteriorating glucose homeostasis, and causing insulin resistance (IR). Moreover, deranged regulation of the renin angiotensin aldo-sterone system (RAAS) through loss of Angiotensin II Type 1 receptor downregulation, and negated repression of ETS-1, results in unopposed detrimental Angiotensin II effects, further promoting IR. Finally, loss of BACH1 and SOCS1 repression abolishes cytoprotective, anti-oxidant, anti-apoptotic, and anti-inflammatory cellular pathways, and promotes β-cell loss. In contrast to RAAS inhibitor treatments that further decrease already reduced miR-155 Levels, strategies to increase an ailing miR-155 production in T2DM, e.g., the use of metformin, mineralocorticoid receptor blockers (spironolactone, eplerenone, finerenone), and verapamil, alone or in various combinations, represent current treatment options. In the future, direct tissue delivery of miRNA analogs is likely.
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Affiliation(s)
| | - Alexandra Papadopoulou
- Occupational and Environmental Health Services, Feelgood Lund, Lund 223-63, Skåne, Sweden
| | - Tar-Choon Aw
- Department of Laboratory Medicine, Changi General Hospital, Singapore 529889, Singapore, Singapore
- Department of Medicine, National University of Singapore, Singapore 119228, Singapore, Singapore
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Torres-Paz YE, Gamboa R, Fuentevilla-Álvarez G, Soto ME, González-Moyotl N, Martínez-Alvarado R, Torres-Tamayo M, Ramírez-Marroquín ES, Vásquez-Jiménez X, Sainz-Escarrega V, Huesca-Gómez C. Overexpression of microRNA-21-5p and microRNA-221-5p in Monocytes Increases the Risk of Developing Coronary Artery Disease. Int J Mol Sci 2023; 24:ijms24108641. [PMID: 37239987 DOI: 10.3390/ijms24108641] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 05/05/2023] [Accepted: 05/09/2023] [Indexed: 05/28/2023] Open
Abstract
MicroRNAs (miRs) regulate gene expression at the post-transcriptional level and are found to be present in monocytes. This study aimed to investigate miR-221-5p, miR-21-5p, and miR-155-5p, their expression in monocytes, and their role in coronary arterial disease (CAD). The study population comprised 110 subjects, and RT-qPCR was used to examine the miR-221-5p, miR-21-5p, and miR-155-5p expressions in monocytes. Results: the miR-21-5p (p = 0.001) and miR-221-5p (p < 0.001) expression levels were significantly higher in the CAD group, and the miR-155-5p (p = 0.021) expression levels were significantly lower in the CAD group; only miR-21-5p and miR-221-5p upregulation was found to be associated with an increased CAD risk. The results show significant increases in miR-21-5p in the unmedicated CAD group with the metformin patients vs. the healthy control group (p = 0.001) and vs. the medicated CAD group with metformin (p = 0.022). The same was true for miR-221-5p in the CAD patients unmedicated with metformin vs. the healthy control group (p < 0.001). Our results from Mexican CAD patients show that the overexpression in monocytes of miR-21-5p and miR-221-5p increases the risk of the development of CAD. In addition, in the CAD group, the metformin downregulated the expression of miR-21-5p and miR-221-5p. Also, the expression of endothelial nitric oxide synthase (NOS3) decreased significantly in our patients with CAD, regardless of whether they were medicated. Therefore, our findings allow for the proposal of new therapeutic strategies for the diagnosis and prognosis of CAD and the evaluation of treatment efficacy.
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Affiliation(s)
- Yazmín Estela Torres-Paz
- Physiology Department, Instituto Nacional de Cardiología "Ignacio Chávez", México City 14080, Mexico
- Postgraduate Program in Medical, Dental and Health Sciences, Universidad Nacional Autónoma de México (UNAM), México City 04510, Mexico
| | - Ricardo Gamboa
- Physiology Department, Instituto Nacional de Cardiología "Ignacio Chávez", México City 14080, Mexico
| | - Giovanny Fuentevilla-Álvarez
- Physiology Department, Instituto Nacional de Cardiología "Ignacio Chávez", México City 14080, Mexico
- Biochemistry Department, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional (IPN), México City 11350, Mexico
| | - María Elena Soto
- Immunology Department, Instituto Nacional de Cardiología "Ignacio Chávez", México City 14080, Mexico
| | - Nadia González-Moyotl
- Physiology Department, Instituto Nacional de Cardiología "Ignacio Chávez", México City 14080, Mexico
- Master's Program in Health Science, Escuela Superior de Medicina, Instituto Politécnico Nacional (IPN), México City 11350, Mexico
| | - Rocío Martínez-Alvarado
- Endocrinology Department, Instituto Nacional de Cardiología "Ignacio Chávez", México City 14080, Mexico
| | - Margarita Torres-Tamayo
- Endocrinology Department, Instituto Nacional de Cardiología "Ignacio Chávez", México City 14080, Mexico
| | | | - Xicoténcatl Vásquez-Jiménez
- Cardiothoracic Surgery Department, Instituto Nacional de Cardiología "Ignacio Chávez", México City 14080, Mexico
| | - Víctor Sainz-Escarrega
- Cardiothoracic Surgery Department, Instituto Nacional de Cardiología "Ignacio Chávez", México City 14080, Mexico
| | - Claudia Huesca-Gómez
- Physiology Department, Instituto Nacional de Cardiología "Ignacio Chávez", México City 14080, Mexico
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10
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Ran T, Chen J, Cheng Y, Zhang M, Mao M, Xiang R, Zuo Z, Chang J, Han B, Ma K. A meta-analysis of the relationship between circulating microRNA-155 and coronary artery disease. PLoS One 2023; 18:e0274277. [PMID: 37053299 PMCID: PMC10101406 DOI: 10.1371/journal.pone.0274277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 08/24/2022] [Indexed: 04/15/2023] Open
Abstract
OBJECTIVE Coronary artery disease (CAD) is a leading cause of death worldwide. Many studies in China and abroad have reported an association between the expression level of microRNA-155 and CAD; however, the results remain controversial. We aimed to comprehensively investigate this association based on a meta-analysis. METHODS We first systematically searched eight Chinese and English databases, including China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, PubMed, Web of Science, Embase, Google Scholar, and Cochrane Library, to identify studies concerning the relationship between microRNA-155 levels and CAD published before February 7, 2021. The quality of the literature was assessed by the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using a random-effects model to calculate the standard mean difference with a 95% confidence interval (CI). RESULTS Sixteen articles with a total of 2069 patients with CAD and 1338 controls were included. All the articles were of high quality according to the NOS. The meta-analysis showed that the mean level of microRNA-155 was significantly lower in patients with CAD than in controls. Based on subgroup analyses, the level of microRNA-155 in the plasma of CAD patients and in acute myocardial infarction (AMI) patients was significantly lower than that in controls, whereas this level in CAD patients with mild stenosis was significantly higher than that in controls. CONCLUSION Our study indicates that the expression level of circulating microRNA-155 in patients with CAD is lower than that in a non-CAD group, suggesting a new possible reference index for the diagnosis and monitoring of patients with CAD.
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Affiliation(s)
- Tao Ran
- The First Clinical College, Chongqing Medical University, Chongqing, China
| | - Jinyao Chen
- The First Clinical College, Chongqing Medical University, Chongqing, China
| | - Yu Cheng
- Department of Nursing, University Town Hospital Affiliated to Chongqing Medical University, Chongqing, China
| | - Min Zhang
- School of Public Health and Management, Chongqing Medical University, Chongqing, China
| | - Min Mao
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Rui Xiang
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhong Zuo
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jing Chang
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Baoru Han
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Kanghua Ma
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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11
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Liu P, Wang S, Wang G, Zhao M, Du F, Li K, Wang L, Wu H, Chen J, Yang Y, Su G. Macrophage-derived exosomal miR-4532 promotes endothelial cells injury by targeting SP1 and NF-κB P65 signalling activation. J Cell Mol Med 2022; 26:5165-5180. [PMID: 36071548 PMCID: PMC9575109 DOI: 10.1111/jcmm.17541] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 08/01/2022] [Accepted: 08/26/2022] [Indexed: 11/27/2022] Open
Abstract
Atherosclerosis is a complex pathological process involving macrophages, endothelial cells and vascular smooth muscle cells that can lead to ischemic heart disease; however, the mechanisms underlying cell‐to‐cell communication in atherosclerosis are poorly understood. In this study, we focused on the role of exosomal miRNAs in crosstalk between macrophages and endothelial cells and explored the rarely studied molecular mechanisms involved. Our in vitro result showed that macrophage‐derived exosomal miR‐4532 significantly disrupted human umbilical vein endothelial cells (HUVECs) function by targeting SP1 and downstream NF‐κB P65 activation. In turn, increased endothelin‐1 (ET‐1), intercellular cell adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) and decreased endothelial nitric oxide synthase (eNOS) expression in HUVECs increased attraction of macrophages, exacerbating foam cell formation and transfer of exosomal miR‐4532 to HUVECs. MiR‐4532 overexpression significantly promoted endothelial injury and pretreatment with an inhibitor of miR‐4532 or GW4869 (exosome inhibitor) could reverse this injury. In conclusion, our data reveal that exosomes have a critical role in crosstalk between HUVECs and macrophages. Further, exosomal miR‐4532 transferred from macrophages to HUVECs and targeting specificity protein 1 (SP1) may be a novel therapeutic target in patients with atherosclerosis.
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Affiliation(s)
- Peng Liu
- Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Shuya Wang
- Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Guangxin Wang
- Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Mingming Zhao
- Research Center of Translational Medicine, Jinan Central Hospital, Cheeloo College Shandong University, Jinan, Shandong, China
| | - Fengli Du
- Shandong Provincial Public Health Clinical Center, Jinan, Shandong, China
| | - Kaiyuan Li
- Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Lei Wang
- Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Huihui Wu
- Research Center of Translational Medicine, Jinan Central Hospital, Cheeloo College Shandong University, Jinan, Shandong, China
| | - Jiamin Chen
- Research Center of Translational Medicine, Jinan Central Hospital, Cheeloo College Shandong University, Jinan, Shandong, China
| | - Yang Yang
- Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Guohai Su
- Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
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12
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Decoding microRNA drivers in Atherosclerosis. Biosci Rep 2022; 42:231479. [PMID: 35758143 PMCID: PMC9289798 DOI: 10.1042/bsr20212355] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 05/17/2022] [Accepted: 06/26/2022] [Indexed: 11/17/2022] Open
Abstract
An estimated 97% of the human genome consists of non-protein-coding sequences. As our understanding of genome regulation improves, this has led to the characterization of a diverse array of non-coding RNAs (ncRNA). Among these, micro-RNAs (miRNAs) belong to the short ncRNA class (22–25 nucleotides in length), with approximately 2500 miRNA genes encoded within the human genome. From a therapeutic perspective, there is interest in exploiting miRNA as biomarkers of disease progression and response to treatments, as well as miRNA mimics/repressors as novel medicines. miRNA have emerged as an important class of RNA master regulators with important roles identified in the pathogenesis of atherosclerotic cardiovascular disease. Atherosclerosis is characterized by a chronic inflammatory build-up, driven largely by low-density lipoprotein cholesterol accumulation within the artery wall and vascular injury, including endothelial dysfunction, leukocyte recruitment and vascular remodelling. Conventional therapy focuses on lifestyle interventions, blood pressure-lowering medications, high-intensity statin therapy and antiplatelet agents. However, a significant proportion of patients remain at increased risk of cardiovascular disease. This continued cardiovascular risk is referred to as residual risk. Hence, a new drug class targeting atherosclerosis could synergise with existing therapies to optimise outcomes. Here, we review our current understanding of the role of ncRNA, with a focus on miRNA, in the development and progression of atherosclerosis, highlighting novel biological mechanisms and therapeutic avenues.
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13
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Abstract
Atherosclerotic cardiovascular disease (ASCVD) proceeds through a series of stages: initiation, progression (or regression), and complications. By integrating known biology regarding molecular signatures of each stage with recent advances in high-dimensional molecular data acquisition platforms (to assay the genome, epigenome, transcriptome, proteome, metabolome, and gut microbiome), snapshots of each phase of atherosclerotic cardiovascular disease development can be captured. In this review, we will summarize emerging approaches for assessment of atherosclerotic cardiovascular disease risk in humans using peripheral blood molecular signatures and molecular imaging approaches. We will then discuss the potential (and challenges) for these snapshots to be integrated into a personalized movie providing dynamic readouts of an individual's atherosclerotic cardiovascular disease risk status throughout the life course.
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Affiliation(s)
- Matthew Nayor
- Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Kemar J. Brown
- Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Ramachandran S. Vasan
- Sections of Preventive Medicine & Epidemiology, and Cardiology, Department of Medicine, Boston University School of Medicine, Boston, MA; Department of Epidemiology, Boston University School of Public Health; Boston University Center for Computing and Data Sciences
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14
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Kibel A, Lukinac AM, Dambic V, Juric I, Selthofer-Relatic K. Oxidative Stress in Ischemic Heart Disease. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:6627144. [PMID: 33456670 PMCID: PMC7785350 DOI: 10.1155/2020/6627144] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 11/27/2020] [Accepted: 12/07/2020] [Indexed: 02/06/2023]
Abstract
One of the novel interesting topics in the study of cardiovascular disease is the role of the oxidation system, since inflammation and oxidative stress are known to lead to cardiovascular diseases, their progression and complications. During decades of research, many complex interactions between agents of oxidative stress, oxidation, and antioxidant systems have been elucidated, and numerous important pathophysiological links to na number of disorders and diseases have been established. This review article will present the most relevant knowledge linking oxidative stress to vascular dysfunction and disease. The review will focus on the role of oxidative stress in endotheleial dysfunction, atherosclerosis, and other pathogenetic processes and mechanisms that contribute to the development of ischemic heart disease.
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Affiliation(s)
- Aleksandar Kibel
- Department for Heart and Vascular Diseases, Osijek University Hospital, Osijek, Croatia
- Department of Physiology and Immunology, Faculty of Medicine, University J.J. Strossmayer in Osijek, Osijek, Croatia
| | - Ana Marija Lukinac
- Department of Rheumatology and Clinical Immunology, Osijek University Hospital, Osijek, Croatia
- Faculty of Medicine, University J.J. Strossmayer in Osijek, Osijek, Croatia
| | - Vedran Dambic
- Faculty of Medicine, University J.J. Strossmayer in Osijek, Osijek, Croatia
- Department for Emergency Medical Services of the Osijek-Baranja county, Osijek, Croatia
| | - Iva Juric
- Department for Heart and Vascular Diseases, Osijek University Hospital, Osijek, Croatia
- Department of Internal Medicine, Faculty of Medicine, University J.J. Strossmayer in Osijek, Osijek, Croatia
| | - Kristina Selthofer-Relatic
- Department for Heart and Vascular Diseases, Osijek University Hospital, Osijek, Croatia
- Department of Internal Medicine, Faculty of Medicine, University J.J. Strossmayer in Osijek, Osijek, Croatia
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15
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Barbalata T, Moraru OE, Stancu CS, Devaux Y, Simionescu M, Sima AV, Niculescu LS. Increased miR-142 Levels in Plasma and Atherosclerotic Plaques from Peripheral Artery Disease Patients with Post-Surgery Cardiovascular Events. Int J Mol Sci 2020; 21:ijms21249600. [PMID: 33339419 PMCID: PMC7766790 DOI: 10.3390/ijms21249600] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/12/2020] [Accepted: 12/15/2020] [Indexed: 12/21/2022] Open
Abstract
There is an intensive effort to identify biomarkers to predict cardiovascular disease evolution. We aimed to determine the potential of microRNAs to predict the appearance of cardiovascular events (CVEs) in patients with peripheral artery disease (PAD) following femoral artery bypass surgery. Forty-seven PAD patients were enrolled and divided into two groups, without CVEs (n = 35) and with CVEs (n = 12), during 1 year follow-up. Intra-surgery atherosclerotic plaques from femoral arteries were collected and the levels of miR-142, miR-223, miR-155, and miR-92a of the primary transcripts of these microRNAs (pri-miRNAs), and gene expression of Drosha and Dicer were determined. Results showed that, in the plaques, miR-142, miR-223, and miR-155 expression levels were significantly increased in PAD patients with CVEs compared to those without CVEs. Positive correlations between these miRNAs and their pri-miRNAs levels and the Dicer/Drosha expression were observed. In the plasma of PAD patients with CVEs compared to those without CVEs, miR-223 and miR-142 were significantly increased. The multiple linear regression analyses revealed significant associations among several plasma lipids, oxidative and inflammatory parameters, and plasma miRNAs levels. Receiver operator characteristic (ROC) analysis disclosed that plasma miR-142 levels could be an independent predictor for CVEs in PAD patients. Functional bioinformatics analyses supported the role of these miRNAs in the regulation of biological processes associated with atherosclerosis. Taken together, these data suggest that plasma levels of miR-142, miR-223, miR-155, and miR-92a can significantly predict CVEs among PAD patients with good accuracy, and that plasma levels of miR-142 can be an independent biomarker to predict post-surgery CVEs development in PAD patients.
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Affiliation(s)
- Teodora Barbalata
- Lipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, Romania; (T.B.); (C.S.S.); (M.S.); (A.V.S.)
| | - Oriana E. Moraru
- Emergency Clinical Hospital “Prof. Dr. Agrippa Ionescu”, 149 I.C. Brătianu Street, 077015 Baloteşti, Ilfov County, Romania;
| | - Camelia S. Stancu
- Lipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, Romania; (T.B.); (C.S.S.); (M.S.); (A.V.S.)
| | - Yvan Devaux
- Cardiovascular Research Unit, Luxembourg Institute of Health, L-1445 Strassen, Luxembourg;
| | - Maya Simionescu
- Lipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, Romania; (T.B.); (C.S.S.); (M.S.); (A.V.S.)
| | - Anca V. Sima
- Lipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, Romania; (T.B.); (C.S.S.); (M.S.); (A.V.S.)
| | - Loredan S. Niculescu
- Lipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, Romania; (T.B.); (C.S.S.); (M.S.); (A.V.S.)
- Correspondence:
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16
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Ziaee S, Hosseindokht M, Cheraghi S, Pourgholi L, Ahmadi A, Sadeghian S, Abbasi SH, Davarpasand T, Boroumand M. Predictive Inflammation-related microRNAs for Cardiovascular Events Following Early-Onset Coronary Artery Disease. Arch Med Res 2020; 52:69-75. [PMID: 33261889 DOI: 10.1016/j.arcmed.2020.10.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 09/20/2020] [Accepted: 10/01/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND Early-onset coronary artery disease (EOCAD) increases the risk of major cardiac adverse events (MACE) at the level of safety/effectiveness-related events. Since adverse events affect the quality of life of young patients with EOCAD, MACE prediction is of great importance for improving medical decision-making. AIMS OF THE STUDY We sought to determine whether the most important inflammation-related microRNAs in atherogenesis could predict MACE among patients with EOCAD. METHODS This nested case-control study recruited 143 young patients (males ≤45 and females ≤55 years old), selected from a cohort of patients with premature coronary atherosclerosis at a median follow-up period of 64.1 months. Total RNAs were extracted from their peripheral blood mononuclear cells. The expression levels of 18 miRNAs, which are involved in inflammation and atherogenesis, were analyzed via quantitative reverse transcription PCR. RESULTS A scoring model based on the upregulation of miR-146a_1 and miR-342_1, along with a history of myocardial infarction and the chronic usage of antithrombotic drugs, was able to predict MI/death at the level of safety-related events (higher vs lower risk scores: sHR: 4.61, 95% CI: 1.57-13.57, and p = 0.005). Another prediction model based on the downregulation of miR-145_1, age, and a history of unstable angina was also able to predict revascularization at the level of effectiveness-related events (higher vs lower risk scores: sHR: 2.90, 95% CI: 1.49-5.66, and p = 0.002). CONCLUSIONS Our results highlighted the role of miRNAs in adverse cardiac events and suggest that miR-146a_1, miR-342_1, and miR-145_1 may be useful biomarkers in predictive and preventive cardiology.
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Affiliation(s)
- Shayan Ziaee
- Department of Molecular Pathology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Hosseindokht
- Department of Molecular Pathology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Sara Cheraghi
- Department of Molecular Pathology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Leyla Pourgholi
- Department of Molecular Pathology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Ahmadi
- Faculty of Science, Department of Biology, Persian Gulf University, Bushehr, Iran
| | - Saeed Sadeghian
- Cardiovascular Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Hesameddin Abbasi
- Cardiovascular Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Tahereh Davarpasand
- Cardiovascular Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammadali Boroumand
- Department of Pathology and Laboratory Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
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17
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Ling H, Guo Z, Du S, Liao Y, Li Y, Ding C, Song C. Serum exosomal miR-122-5p is a new biomarker for both acute coronary syndrome and underlying coronary artery stenosis. Biomarkers 2020; 25:539-547. [PMID: 32723190 DOI: 10.1080/1354750x.2020.1803963] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE Acute coronary syndrome presents as unstable angina (UA) or acute myocardial infarction (AMI). We explored the use of exosomal miR-122-5p as a biomarker for UA and AMI and determined whether its expression level is positively correlated with the severity of coronary stenosis. METHODS This study enrolled 34 patients with AMI, 31 patients with UA, and 22 control subjects. qPCR was used to detect the expression levels of serum exosomal miR-122-5p. RESULTS The expression of serum exosomal miR-122-5p in UA and AMI patients was significantly higher than that in the control group, and expression levels differed between UA and AMI patients. Receiver operating characteristic analysis demonstrated that serum exosomal miR-122-5p might be used as a diagnostic biomarker for AMI and UA. In addition, we also found that serum exosomal miR-122-5p was positively correlated with the severity of coronary artery stenosis for UA patients based on the Gensini score. Serum exosomal miR-122-5p was highly expressed in patients with a coronary artery stenosis severity greater than 80% during acute coronary syndrome. CONCLUSION Serum exosomal miR-122-5p might be useful as a diagnostic biomarker for AMI and UA, and increased serum exosomal miR-122-5p levels could be useful to predict the severity of coronary lesions.
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Affiliation(s)
- Hao Ling
- Department of Cardiology, Second Hospital of Jilin University, Chang Chun, China
| | - Ziyuan Guo
- Department of Cardiology, Second Hospital of Jilin University, Chang Chun, China
| | - Shuangshuang Du
- Department of Cardiology, Second Hospital of Jilin University, Chang Chun, China
| | - Yinghong Liao
- Department of Cardiology, Second Hospital of Jilin University, Chang Chun, China
| | - Yunyan Li
- Department of Cardiology, Second Hospital of Jilin University, Chang Chun, China
| | - Chao Ding
- Department of Cardiology, Second Hospital of Jilin University, Chang Chun, China
| | - Chunli Song
- Department of Cardiology, Second Hospital of Jilin University, Chang Chun, China
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18
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Fasolo F, Di Gregoli K, Maegdefessel L, Johnson JL. Non-coding RNAs in cardiovascular cell biology and atherosclerosis. Cardiovasc Res 2020; 115:1732-1756. [PMID: 31389987 DOI: 10.1093/cvr/cvz203] [Citation(s) in RCA: 143] [Impact Index Per Article: 28.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 07/14/2019] [Accepted: 08/05/2019] [Indexed: 02/07/2023] Open
Abstract
Atherosclerosis underlies the predominant number of cardiovascular diseases and remains a leading cause of morbidity and mortality worldwide. The development, progression and formation of clinically relevant atherosclerotic plaques involves the interaction of distinct and over-lapping mechanisms which dictate the roles and actions of multiple resident and recruited cell types including endothelial cells, vascular smooth muscle cells, and monocyte/macrophages. The discovery of non-coding RNAs (ncRNAs) including microRNAs, long non-coding RNAs, and circular RNAs, and their identification as key mechanistic regulators of mRNA and protein expression has piqued interest in their potential contribution to atherosclerosis. Accruing evidence has revealed ncRNAs regulate pivotal cellular and molecular processes during all stages of atherosclerosis including cell invasion, growth, and survival; cellular uptake and efflux of lipids, expression and release of pro- and anti-inflammatory intermediaries, and proteolytic balance. The expression profile of ncRNAs within atherosclerotic lesions and the circulation have been determined with the aim of identifying individual or clusters of ncRNAs which may be viable therapeutic targets alongside deployment as biomarkers of atherosclerotic plaque progression. Consequently, numerous in vivo studies have been convened to determine the effects of moderating the function or expression of select ncRNAs in well-characterized animal models of atherosclerosis. Together, clinicopathological findings and studies in animal models have elucidated the multifaceted and frequently divergent effects ncRNAs impose both directly and indirectly on the formation and progression of atherosclerosis. From these findings' potential novel therapeutic targets and strategies have been discovered which may pave the way for further translational studies and possibly taken forward for clinical application.
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Affiliation(s)
- Francesca Fasolo
- Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar-Technical University Munich, Biedersteiner Strasse 29, Munich, Germany
| | - Karina Di Gregoli
- Laboratory of Cardiovascular Pathology, Bristol Medical School, University of Bristol, Bristol, UK
| | - Lars Maegdefessel
- Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar-Technical University Munich, Biedersteiner Strasse 29, Munich, Germany.,Molecular Vascular Medicine, Karolinska Institute, Center for Molecular Medicine L8:03, 17176 Stockholm, Sweden.,German Center for Cardiovascular Research (DZHK), Partner Site Munich (Munich Heart Alliance), Munich, Germany
| | - Jason L Johnson
- Laboratory of Cardiovascular Pathology, Bristol Medical School, University of Bristol, Bristol, UK
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Oxidative Stress and New Pathogenetic Mechanisms in Endothelial Dysfunction: Potential Diagnostic Biomarkers and Therapeutic Targets. J Clin Med 2020; 9:jcm9061995. [PMID: 32630452 PMCID: PMC7355625 DOI: 10.3390/jcm9061995] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 06/15/2020] [Accepted: 06/23/2020] [Indexed: 02/07/2023] Open
Abstract
Cardiovascular diseases (CVD), including heart and pathological circulatory conditions, are the world's leading cause of mortality and morbidity. Endothelial dysfunction involved in CVD pathogenesis is a trigger, or consequence, of oxidative stress and inflammation. Endothelial dysfunction is defined as a diminished production/availability of nitric oxide, with or without an imbalance between endothelium-derived contracting, and relaxing factors associated with a pro-inflammatory and prothrombotic status. Endothelial dysfunction-induced phenotypic changes include up-regulated expression of adhesion molecules and increased chemokine secretion, leukocyte adherence, cell permeability, low-density lipoprotein oxidation, platelet activation, and vascular smooth muscle cell proliferation and migration. Inflammation-induced oxidative stress results in an increased accumulation of reactive oxygen species (ROS), mainly derived from mitochondria. Excessive ROS production causes oxidation of macromolecules inducing cell apoptosis mediated by cytochrome-c release. Oxidation of mitochondrial cardiolipin loosens cytochrome-c binding, thus, favoring its cytosolic release and activation of the apoptotic cascade. Oxidative stress increases vascular permeability, promotes leukocyte adhesion, and induces alterations in endothelial signal transduction and redox-regulated transcription factors. Identification of new endothelial dysfunction-related oxidative stress markers represents a research goal for better prevention and therapy of CVD. New-generation therapeutic approaches based on carriers, gene therapy, cardiolipin stabilizer, and enzyme inhibitors have proved useful in clinical practice to counteract endothelial dysfunction. Experimental studies are in continuous development to discover new personalized treatments. Gene regulatory mechanisms, implicated in endothelial dysfunction, represent potential new targets for developing drugs able to prevent and counteract CVD-related endothelial dysfunction. Nevertheless, many challenges remain to overcome before these technologies and personalized therapeutic strategies can be used in CVD management.
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20
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Ling H, Guo Z, Shi Y, Zhang L, Song C. Serum Exosomal MicroRNA-21, MicroRNA-126, and PTEN Are Novel Biomarkers for Diagnosis of Acute Coronary Syndrome. Front Physiol 2020; 11:654. [PMID: 32595526 PMCID: PMC7300246 DOI: 10.3389/fphys.2020.00654] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 05/22/2020] [Indexed: 12/14/2022] Open
Abstract
Acute coronary syndrome (ACS) is a serious threat to public health. Based on clinical manifestations, ACS can be classified into unstable angina (UA) pectoris and acute myocardial infarction (AMI). The purpose of this study was to explore the possibility of using serum exosomal microRNA (miR)-126, miR-21, and phosphatase and tensin homolog (PTEN) expression levels as biomarkers of UA and AMI and to investigate whether these levels were positively correlated with the severity of coronary stenosis based on the Gensini score. Exosomes were isolated by ultracentrifugation from the serum of 34 patients with AMI, 31 patients with UA, and 22 healthy controls. The isolated exosomes were characterized by electron microscopy and particle size analysis; exosomal identity was further confirmed by western blotting using exosome-specific antibodies. Real-time quantitative polymerase chain reaction indicated that the serum exosomal levels of miR-126 and miR-21 were significantly higher in the patients with UA and AMI than in the healthy controls. Enzyme-linked immunosorbent assay showed that the serum exosomal PTEN levels were significantly higher in the UA and AMI groups than in the control group. Receiving operating characteristic curve analysis demonstrated the diagnostic efficiency of serum exosomal miR-126, miR-21, and PTEN levels for predicting AMI and UA. In addition, the circulating exosomal miR-126 level was positively correlated with the severity of coronary artery stenosis in patients with UA and AMI based on the Gensini score.
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Affiliation(s)
- Hao Ling
- Department of Cardiology, The Second Hospital of Jilin University, Changchun, China
| | - Ziyuan Guo
- Department of Cardiology, The Second Hospital of Jilin University, Changchun, China
| | - Yongfeng Shi
- Department of Cardiology, The Second Hospital of Jilin University, Changchun, China
| | - Lei Zhang
- Department of Neurology, The Second Hospital of Jilin University, Changchun, China
| | - Chunli Song
- Department of Cardiology, The Second Hospital of Jilin University, Changchun, China
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21
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Ruan Z, Chu T, Wu L, Zhang M, Zheng M, Zhang Q, Zhou M, Zhu G. miR-155 inhibits oxidized low-density lipoprotein-induced apoptosis in different cell models by targeting the p85α/AKT pathway. J Physiol Biochem 2020; 76:329-343. [PMID: 32277342 DOI: 10.1007/s13105-020-00738-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Accepted: 03/26/2020] [Indexed: 12/17/2022]
Abstract
The apoptosis of vascular endothelial cells (VECs), vascular smooth muscle cells (VSMCs), and macrophages directly causes the instability or rupture of atherosclerotic plaques. Accumulating evidence suggests that oxidized low-density lipoprotein (OxLDL) could induce apoptosis via endogenous or exogenous pathways. Interestingly, it has been reported that microRNA155 (miR-155) plays a pivotal role in the regulation of apoptosis. Here, we hypothesized that overexpression of miR-155 could inhibit OxLDL-induced apoptosis by targeting the p85α/AKT pathway. In this study, we established models of OxLDL-induced apoptosis in mouse VECs, VSMCs, and macrophages. Furthermore, we explored the effects of miR-155 expression on the apoptosis of different cells, and ultimately revealed whether miR-155 regulated apoptosis by targeting the p85α/AKT pathway. The results demonstrated that miR-155 inhibited p85α expression and attenuated VEC, VSMC, and macrophage apoptosis, at least in part by suppressing the expression of p85α-activated AKT to inhibit apoptosis. Our findings collectively suggested that miR-155 attenuated OxLDL-mediated apoptosis in different cells by targeting p85α, supporting its possible therapeutic role in atherosclerosis.
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Affiliation(s)
- Zhimin Ruan
- Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China
| | - Tianshu Chu
- Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China
| | - Liyong Wu
- Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China
| | - Mingguo Zhang
- Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China
| | - Mei Zheng
- Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China
| | - Qian Zhang
- Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China
| | - Mingli Zhou
- Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China
| | - Guofu Zhu
- Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China.
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Noncoding RNAs as Biomarkers for Acute Coronary Syndrome. BIOMED RESEARCH INTERNATIONAL 2020; 2020:3298696. [PMID: 32337239 PMCID: PMC7154975 DOI: 10.1155/2020/3298696] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Revised: 03/18/2020] [Accepted: 03/24/2020] [Indexed: 12/17/2022]
Abstract
Acute coronary syndrome (ACS), consisting of acute myocardial infarction and unstable angina, is the most dangerous and fatal form of coronary heart disease. Acute coronary syndrome has sudden onset and rapid development, which may lead to malignant life-threatening conditions at any time. Therefore, early detection and diagnosis are critical for patients with ACS. Recent studies have found that noncoding RNA is of great significance in the diagnosis and treatment of cardiovascular diseases. In this review, we summarized recent data on circulating noncoding RNAs (including microRNA, long noncoding RNA, and circular RNA) as diagnostic and prognostic markers in ACS including acute myocardial infarction and unstable angina. Specifically, microRNAs (miRNAs) as diagnostic markers are divided into three types: miRNAs of increased expression in ACS, miRNAs of decreased expression in ACS, and miRNAs of contradictory expression in ACS. Moreover, we described these miRNAs of increased expression in ACS based on miRNAs family. This review may result in a great guidance of noncoding RNAs as biomarkers for ACS in clinical practice.
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Schiano C, Benincasa G, Franzese M, Della Mura N, Pane K, Salvatore M, Napoli C. Epigenetic-sensitive pathways in personalized therapy of major cardiovascular diseases. Pharmacol Ther 2020; 210:107514. [PMID: 32105674 DOI: 10.1016/j.pharmthera.2020.107514] [Citation(s) in RCA: 89] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The complex pathobiology underlying cardiovascular diseases (CVDs) has yet to be explained. Aberrant epigenetic changes may result from alterations in enzymatic activities, which are responsible for putting in and/or out the covalent groups, altering the epigenome and then modulating gene expression. The identification of novel individual epigenetic-sensitive trajectories at single cell level might provide additional opportunities to establish predictive, diagnostic and prognostic biomarkers as well as drug targets in CVDs. To date, most of studies investigated DNA methylation mechanism and miRNA regulation as epigenetics marks. During atherogenesis, big epigenetic changes in DNA methylation and different ncRNAs, such as miR-93, miR-340, miR-433, miR-765, CHROME, were identified into endothelial cells, smooth muscle cells, and macrophages. During man development, lipid metabolism, inflammation and homocysteine homeostasis, alter vascular transcriptional mechanism of fundamental genes such as ABCA1, SREBP2, NOS, HIF1. At histone level, increased HDAC9 was associated with matrix metalloproteinase 1 (MMP1) and MMP2 expression in pro-inflammatory macrophages of human carotid plaque other than to have a positive effect on toll like receptor signaling and innate immunity. HDAC9 deficiency promoted inflammation resolution and reverse cholesterol transport, which might block atherosclerosis progression and promote lesion regression. Here, we describe main human epigenetic mechanisms involved in atherosclerosis, coronary heart disease, ischemic stroke, peripheral artery disease; cardiomyopathy and heart failure. Different epigenetics mechanisms are activated, such as regulation by circular RNAs, as MICRA, and epitranscriptomics at RNA level. Moreover, in order to open new frontiers for precision medicine and personalized therapy, we offer a panoramic view on the most innovative bioinformatic tools designed to identify putative genes and molecular networks underlying CVDs in man.
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Affiliation(s)
- Concetta Schiano
- Clinical Department of Internal Medicine and Specialistics, Department of Advanced Clinical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
| | - Giuditta Benincasa
- Clinical Department of Internal Medicine and Specialistics, Department of Advanced Clinical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | | | | | | | | | - Claudio Napoli
- Clinical Department of Internal Medicine and Specialistics, Department of Advanced Clinical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy; IRCCS SDN, Naples, Italy
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Sanlialp M, Dodurga Y, Uludag B, Alihanoglu YI, Enli Y, Secme M, Bostanci HE, Cetin Sanlialp S, Tok OO, Kaftan A, Kilic ID. Peripheral blood mononuclear cell microRNAs in coronary artery disease. J Cell Biochem 2019; 121:3005-3009. [PMID: 31788836 DOI: 10.1002/jcb.29557] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2012] [Accepted: 10/04/2013] [Indexed: 11/11/2022]
Abstract
The accuracy of risk prediction for coronary artery disease can be improved with the use of novel molecular or genetic biomarkers. In this study, we investigated the difference of five selected microRNAs (miR or miRNA) in patients with coronary artery disease (CAD) and controls, assessed by coronary angiography. The study population consisted of 85 subjects, aged between 18 and 75 years and underwent invasive coronary angiography. Subjects with more than 30% stenosis in at least one coronary artery, patients with a history of prior percutaneous coronary intervention or coronary by-pass surgery were allocated to the patient group; whereas the subjects without at least 30% stenosis consisted the control group. Groups were similar in age, presence of hypertension, and smoking status. However, the proportion of males and subjects taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta blockers, nitrates, and statins were higher in the patient group. miR-221 and miR-155 were downregulated (P = .02 and .001, respectively), while miR-21 levels were significantly increased (P = .003) in the patient group compared to controls. Changes in miR-145 and miR-126 did not reach statistical significance (P > .05). miRNA- 21, miR-155, and miR-221 were differentially expressed between the patients and controls. miRNAs are promising biomarkers for CAD diagnosis, however, this requires further research with larger groups.
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Affiliation(s)
- Musa Sanlialp
- Department of Cardiology, Tavas State Hospital, Denizli, Turkey
| | - Yavuz Dodurga
- Department of Medical Biology and Genetics, School of Medicine, Pamukkale University, Denizli, Turkey
| | - Burcu Uludag
- Department of Cardiology, Dr. Suat Seren Chest Hospital, Izmir, Turkey
| | | | - Yasar Enli
- Department of Biochemistry, Faculty of Medicine, Pamukkale University, Denizli, Turkey
| | - Mucahit Secme
- Department of Medical Biology and Genetics, School of Medicine, Pamukkale University, Denizli, Turkey
| | - Hayrani Eren Bostanci
- Department of Biochemistry, Faculty of Medicine, Pamukkale University, Denizli, Turkey
| | | | - Ozge Ozden Tok
- Department of Cardiology, Bahcelievler Memorial Hospital, Istanbul, Turkey
| | - Asuman Kaftan
- Department of Cardiology, Pamukkale University Hospital, Denizli, Turkey
| | - Ismail Dogu Kilic
- Department of Cardiology, Pamukkale University Hospital, Denizli, Turkey
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Inflammation-Related MicroRNAs Are Associated with Plaque Stability Calculated by IVUS in Coronary Heart Disease Patients. J Interv Cardiol 2019; 2019:9723129. [PMID: 31866771 PMCID: PMC6915018 DOI: 10.1155/2019/9723129] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Revised: 08/24/2019] [Accepted: 09/24/2019] [Indexed: 02/08/2023] Open
Abstract
Objectives This study aimed to investigate the association between inflammation-related microRNAs (miR-21, 146a, 155) and the plaque stability in coronary artery disease patients. Methods The expression of miR-21, 146a, and 155 was measured by real-time PCR in 310 consecutive patients. The level of hs-CRP, IL-6, and IL-8 was measured by ELISA. The plaque stability of coronary stenotic lesions was evaluated with intravascular ultrasound (IVUS). Results (1) The levels of hs-CRP, IL-6, and IL-8 were significantly increased in the UAP and AMI groups compared with the CPS group (P < 0.01). (2) The expression of miR-21 and miR-146a in peripheral blood mononuclear cells (PBMCs) and plasma was significantly higher in CAD patients compared with non-CAD patients, whereas the miR-155 expression in PBMCs and plasma was significantly lower in patients with CAD. (3) The miR-21 expression in PBMCs was higher in UAP and AMI groups compared with CPS group. The miR-146a expression in PBMCs was higher in SAP, UAP, and AMI groups than in CPS group. Although the level of miR-155 in PBMCs was lower in SAP, UAP, and AMI groups than in CPS group. The expression patterns of miR-21, miR-146a, and miR-155 in plasma were consistent with those of PBMCs. (4) The expressions of miR-21 and miR-146a in PBMCs and plasma were significantly higher in the vulnerable plaque group than those in stable plaque group. While miR-155 in PBMCs and plasma was significantly lower in vulnerable plaque group compared with stable plaque group. (5) The levels of miR-21 and miR-146a in PBMCs and plasma were significantly higher in soft plaque group than in fibrous plaque group and calcified plaque group. However, miR-155 in PBMCs and plasma was significantly lower in soft plaque group. Conclusions The expression of miR-21 and miR-146a are associated with the plaque stability in coronary stenotic lesions, whereas miR-155 expression is inversely associated with the plaque stability.
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Kukava NG, Shkhnovich RM, Osmak GZ, Baulina NM, Matveeva NA, Favorova OO. [The Role of microRNA in the Development of Ischemic Heart Disease]. ACTA ACUST UNITED AC 2019; 59:78-87. [PMID: 31615390 DOI: 10.18087/cardio.2019.10.n558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Accepted: 04/29/2019] [Indexed: 11/18/2022]
Abstract
Coronary artery disease is the most clinically significant manifestation of atherosclerosis and the main cause of morbidity and mortality around the world. Atherogenesis is a complex process, involving various types of cells and regulatory molecules. MicroRNA molecules were discovered at the end of the 20th century, and nowadays are the important regulators of several pathophysiological processes of atherogenesis. The review examines data on the participation of various microRNAs in the development of atherosclerosis and its main clinical manifestations and discusses the possibility of using microRNAs as diagnostic markers for these diseases.
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Affiliation(s)
- N G Kukava
- Institute of Clinical Cardiology named after A.L. Myasnikov, National Cardiology Research Center
| | - R M Shkhnovich
- Institute of Clinical Cardiology named after A.L. Myasnikov, National Cardiology Research Center; Medical Academy of Continuing Education Russian Medical Academy of Postgraduate Education
| | - G Z Osmak
- Institute of Experimental Cardiology, National Medical Research Center for Cardiology
| | - N M Baulina
- Institute of Experimental Cardiology, National Medical Research Center for Cardiology
| | - N A Matveeva
- Institute of Experimental Cardiology, National Medical Research Center for Cardiology
| | - O O Favorova
- Institute of Experimental Cardiology, National Medical Research Center for Cardiology
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Rizzacasa B, Amati F, Romeo F, Novelli G, Mehta JL. Epigenetic Modification in Coronary Atherosclerosis. J Am Coll Cardiol 2019; 74:1352-1365. [DOI: 10.1016/j.jacc.2019.07.043] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 07/15/2019] [Indexed: 02/06/2023]
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Johnson JL. Elucidating the contributory role of microRNA to cardiovascular diseases (a review). Vascul Pharmacol 2018; 114:31-48. [PMID: 30389614 PMCID: PMC6445803 DOI: 10.1016/j.vph.2018.10.010] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 07/13/2018] [Accepted: 10/28/2018] [Indexed: 02/07/2023]
Abstract
Cardiovascular diseases encompassing atherosclerosis, aortic aneurysms, restenosis, and pulmonary arterial hypertension, remain the leading cause of morbidity and mortality worldwide. In response to a range of stimuli, the dynamic interplay between biochemical and biomechanical mechanisms affect the behaviour and function of multiple cell types, driving the development and progression of cardiovascular diseases. Accumulating evidence has highlighted microRNAs (miRs) as significant regulators and micro-managers of key cellular and molecular pathophysiological processes involved in predominant cardiovascular diseases, including cell mitosis, motility and viability, lipid metabolism, generation of inflammatory mediators, and dysregulated proteolysis. Human pathological and clinical studies have aimed to identify select microRNA which may serve as biomarkers of disease and their progression, which are discussed within this review. In addition, I provide comprehensive coverage of in vivo investigations elucidating the modulation of distinct microRNA on the pathophysiology of atherosclerosis, abdominal aortic aneurysms, restenosis, and pulmonary arterial hypertension. Collectively, clinical and animal studies have begun to unravel the complex and often diverse effects microRNAs and their targets impart during the development of cardiovascular diseases and revealed promising therapeutic strategies through which modulation of microRNA function may be applied clinically.
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Affiliation(s)
- Jason L Johnson
- Laboratory of Cardiovascular Pathology, Bristol Medical School, University of Bristol, UK.
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Zhao D, Zhao J, Sun J, Su Y, Jian J, Ye H, Lin J, Yang Z, Feng J, Wang Z. The expression level of miR-155 in plasma and peripheral blood mononuclear cells in coronary artery disease patients and the associations of these levels with the apoptosis rate of peripheral blood mononuclear cells. Exp Ther Med 2018; 16:4373-4378. [PMID: 30542386 PMCID: PMC6257726 DOI: 10.3892/etm.2018.6797] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Accepted: 06/28/2018] [Indexed: 01/05/2023] Open
Abstract
The aim of the study was to investigate the expression of miR-155 in plasma and peripheral blood mononuclear cells (PBMCs), the effects of miR-155 on the apoptosis rate of PBMCs and the extent of coronary stenosis in coronary artery disease patients. Seventy chest pain patients were divided into three groups by symptoms, signs, auxiliary examination and coronary arteriography: 21 cases in the acute myocardial infarction group (AMI), 23 cases in the Angor pectoris group (AP) and 26 cases in the control group (CT). The peripheral blood mononuclear cells of the patients in the three groups were separated for cell culture. Annexin V/propidium iodide (PI) was performed to analyze cell apoptosis. RT-qPCR was used to evaluate the expression level of miR-155 in plasma and PBMCs. There were significant differences on the expression of miR-155 in plasma and PBMCs, the apoptosis rate of PBMCs, Gensini score and the extent of coronary stenosis among the three groups (P<0.05). The expression of miR-155 in plasma and PBMCs in AMI and AP group were lower than CT group while the AMI group was lower than the AP group (P<0.05). The apoptotic rate of PBMCs, Gensini score and the extent of coronary stenosis of the AMI and AP groups were higher than CT group while the AMI group was higher than the AP group (P<0.05). The expression of miR-155 in plasma was positively correlated with PBMCs, but negatively correlated with the apoptosis rate of PBMCs, Gensini score and the extent of coronary stenosis. The apoptosis rate of PBMCs in patients with coronary heart disease was positively correlated with the degree of coronary artery stenosis and Gensini score. In conclusion, in the patients with coronary heart disease the apoptosis rate of PBMCs was increased and the expression of miR-155 in plasma and PBMCs cells was decreased, which were correlated with the severity of coronary heart disease.
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Affiliation(s)
- Duo Zhao
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.,Department of Cardiovascular Surgery, The First People's Hospital of Foshan (Affiliated Foshan Hospital of Sun Yat-sen University), Foshan, Guangdong 528000, P.R. China
| | - Jing Zhao
- Department of Cardiovascular Surgery, The First People's Hospital of Foshan (Affiliated Foshan Hospital of Sun Yat-sen University), Foshan, Guangdong 528000, P.R. China
| | - Jiangbin Sun
- Department of Cardiovascular Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P.R. China
| | - Yanling Su
- Department of Cardiovascular Surgery, The First People's Hospital of Foshan (Affiliated Foshan Hospital of Sun Yat-sen University), Foshan, Guangdong 528000, P.R. China
| | - Jinfeng Jian
- Department of Cardiovascular Surgery, The First People's Hospital of Foshan (Affiliated Foshan Hospital of Sun Yat-sen University), Foshan, Guangdong 528000, P.R. China
| | - Huaan Ye
- Department of Cardiovascular Surgery, The First People's Hospital of Foshan (Affiliated Foshan Hospital of Sun Yat-sen University), Foshan, Guangdong 528000, P.R. China
| | - Jiawang Lin
- Department of Cardiovascular Surgery, The First People's Hospital of Foshan (Affiliated Foshan Hospital of Sun Yat-sen University), Foshan, Guangdong 528000, P.R. China
| | - Zongda Yang
- Department of Cardiovascular Surgery, The First People's Hospital of Foshan (Affiliated Foshan Hospital of Sun Yat-sen University), Foshan, Guangdong 528000, P.R. China
| | - Jiatao Feng
- Department of Cardiovascular Surgery, The First People's Hospital of Foshan (Affiliated Foshan Hospital of Sun Yat-sen University), Foshan, Guangdong 528000, P.R. China
| | - Zhiping Wang
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China
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Abstract
Left ventricular assist device (LVAD) therapy unloads the failing heart but exposes the human body to unique pathophysiologic demands such as continuous blood flow and complete univentricular support, which are associated with increased risk of adverse clinical outcomes. MicroRNAs (miRNAs) are 22-23 nucleotide RNAs involved in regulation of multiple biologic processes including the pathogenesis of heart failure (HF). Thus, measurement of miRNAs may have potential in both diagnostics as circulating biomarkers and in therapeutics for targeted interventions. We examined 23 distinct miRNAs that have previously been shown to play a role in HF pathogenesis and measured them in 40 individuals both before continuous-flow LVAD implantation and at a median of 96.5 days after implantation. Quantitative real-time polymerase chain reaction was performed for miRNA amplification, and 19 miRs were included in statistical analysis. Wilcoxon signed-rank tests were used to compare within-patient median relative quantification values pre- and post-LVAD placement. The median age of patients was 67 years, and 57.5% were at Interagency Registry for Mechanically Assisted Circulatory Support level 1-2. After LVAD support, only miR-155 was found to be statistically significant (p < 0.002), with an upregulation in plasma expression levels with LVAD support, which persisted regardless of the direction of change in serial HF biomarker levels. MicroRNA-155, which has been shown to play a central role in inflammation and neovascularization, was upregulated with long-term LVAD support. If validated by future studies, miR-155 may help further inform on underlying LVAD physiology and has a role as a therapeutic target in this patient population.
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Liu K, Xuekelati S, Zhou K, Yan Z, Yang X, Inayat A, Wu J, Guo X. Expression Profiles of Six Atherosclerosis-Associated microRNAs That Cluster in Patients with Hyperhomocysteinemia: A Clinical Study. DNA Cell Biol 2018; 37:189-198. [PMID: 29461880 DOI: 10.1089/dna.2017.3845] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The aim of this study is to discuss the hypothesis that expression of plasma atherosclerosis-associated microRNAs (miRNAs) in hyperhomocysteinemia (Hhcy) patients could predict the presence of atherosclerosis from different channels. Six plasma miRNAs (miR-145, miR-155, miR-222, miR-133, miR-217, and miR-30) selected for our study have been confirmed as critical gene regulators involved in atherosclerosis and can be steadily determined in plasma. Expression of the above six plasma circulating miRNAs revealed significant upregulation of two miRNAs (miR-133 and miR-217) and downregulation of three miRNAs (miR-145, miR-155, and miR-222). Six candidate miRNAs showed a significant correlation with homocysteine (Hcy) or lipid parameters. The results of this study indicated that miR-217 was further significantly upregulated in Hhcy + ATH groups than in normal control, Hhcy-, and atherosclerosis-alone (ATH) groups and it showed a significant negative correlation with Hcy and triglycerides. More specifically, miR-217 showed the most specific expression patterns in all patients with atherosclerosis (ATH and Hhcy + ATH groups), which may have been a diagnostic value for Hhcy complicated with atherosclerosis, and predicted the progress of atherosclerosis in Hhcy patients effectively.
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Affiliation(s)
- Kejian Liu
- 1 Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China .,2 Department of Cardiology, The First Affiliated Hospital, Shihezi University School of Medicine , Shihezi, China
| | - Saiyare Xuekelati
- 3 The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University , Shihezi, China
| | - Kang Zhou
- 2 Department of Cardiology, The First Affiliated Hospital, Shihezi University School of Medicine , Shihezi, China
| | - Zhitao Yan
- 2 Department of Cardiology, The First Affiliated Hospital, Shihezi University School of Medicine , Shihezi, China
| | - Xu Yang
- 2 Department of Cardiology, The First Affiliated Hospital, Shihezi University School of Medicine , Shihezi, China
| | - Azeem Inayat
- 3 The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University , Shihezi, China
| | - Jiangdong Wu
- 3 The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University , Shihezi, China
| | - Xiaomei Guo
- 1 Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
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Qiu XK, Ma J. Alteration in microRNA-155 level correspond to severity of coronary heart disease. Scandinavian Journal of Clinical and Laboratory Investigation 2018; 78:219-223. [PMID: 29411649 DOI: 10.1080/00365513.2018.1435904] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Cardiovascular diseases are a consequence of genetic and epigenetic interactions. Inflammation contributes toward the initiation and progression of atherosclerotic lesions. Previous studies have shown that microRNA (miR) 155 plays a role in cardiovascular disease, including the prevention of inflammatory infiltration, regulation of autophagy, and participation of immunoreactions. However, the change of miR-155 level in the development of atherosclerosis remains to be determined. The initial objective of this study was that CHD patients would have altered serum miR-155 level. We also aim to identify whether circulating miR-155 content could be used as a predictor for severity of coronary atherosclerosis. Sample was collected from 300 CHD patients and 100 controls. Quantitative real-time PCR analysis was utilized on RNA isolated from plasma. Expression of miR-155 was identified on the basis of the quartiles of the Gensini score, and association between the microRNA and CHD was analyzed. CHD patients had higher miR-155 level in comparison to controls (p < .001), and the miRNA content significantly increased following an increasing Gensini score (p < .001). Gensini score was significantly associated with miR-155 expression (r = 0.6124, p < .001). Our findings suggest that interaction between circulating miR-155 expressions with classical risk factors of atherosclerotic lesions, and serum miR-155 content may serve as a novel biomarker for evaluating severity of CHD.
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Affiliation(s)
- Xian-Ke Qiu
- a Department of Emergency , Wenzhou Central Hospital , Wenzhou , China
| | - Jun Ma
- b Department of Cardiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China
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Klimczak D, Kuch M, Pilecki T, Żochowska D, Wirkowska A, Pączek L. Plasma microRNA-155-5p is increased among patients with chronic kidney disease and nocturnal hypertension. ACTA ACUST UNITED AC 2017; 11:831-841.e4. [PMID: 29146158 DOI: 10.1016/j.jash.2017.10.008] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 10/17/2017] [Accepted: 10/23/2017] [Indexed: 12/13/2022]
Abstract
MicroRNAs play multiple roles in the regulation of blood pressure (BP). Nevertheless, to date, no study has assessed the association between microRNA plasma expression and BP control in chronic kidney disease (CKD) patients. Given this background, we evaluated the plasma expression of miR-155-5p, a translational inhibitor of angiotensin receptor type I, in CKD patients, to determine the association between miR-155-5p level and BP control. In this single-center cross-sectional study, we analyzed the miR-155-5p concentration by quantitative reverse transcriptase polymerase chain reaction using the U6 snRNA as a reference gene and 24-hour ambulatory blood pressure monitoring in CKD patients (stage ≥2) in relation to a control group of healthy age-matched and gender-matched individuals, with normal BP proven by the ambulatory blood pressure monitoring. We enrolled a total of 105 patients with CKD (stages 2-5, including 33 kidney renal transplant recipients), aged 59 ± 14 years; 47% males and 26 healthy volunteers (aged 55 ± 13, 50% male). Within the study group, a total of 36 patients (40%) presented with an average 24-hour systolic BP (SBP) ≥130 mm Hg and 41 patients (45%) presented nocturnal hypertension (NHT; SBP ≥120 mm Hg or diastolic BP ≥ 70 mm Hg). miRNA-155-5p was increased in plasma of CKD patients with median expression relative to control subjects equal to 2.92 (1.34-5.58). Interestingly, the plasma miRNA-155-5p expression was significantly higher in patients with NHT: 4.04 (2.92-10.8) versus 2.01 (1.21-3.07), P = .001 and its expression maintained an independent association with the average nocturnal SBP (coefficient B = 4.368, P = .047) by a multivariate regression analysis adjusted for confounders. The miR-155-5p was increased among CKD patients and further increased among subjects presenting with NHT. Further studies are warranted to determine the role of this non-coding RNA as a potential novel biomarker and therapeutic target in the non-dipping CKD individuals, characterized by increased cardiovascular risk.
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Affiliation(s)
- Dominika Klimczak
- Department of Immunology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland; Department of Heart Failure and Cardiac Rehabilitation, Second Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Marek Kuch
- Department of Cardiology, Hypertension and Internal Medicine, Second Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Tomasz Pilecki
- Department of Immunology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Dorota Żochowska
- Department of Immunology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Agnieszka Wirkowska
- Department of Immunology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Leszek Pączek
- Department of Immunology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
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de Gonzalo-Calvo D, Iglesias-Gutiérrez E, Llorente-Cortés V. Biomarcadores epigenéticos y enfermedad cardiovascular: los microARN circulantes. Rev Esp Cardiol 2017. [DOI: 10.1016/j.recesp.2017.02.027] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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de Gonzalo-Calvo D, Iglesias-Gutiérrez E, Llorente-Cortés V. Epigenetic Biomarkers and Cardiovascular Disease: Circulating MicroRNAs. ACTA ACUST UNITED AC 2017. [PMID: 28623159 DOI: 10.1016/j.rec.2017.05.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
MicroRNAs (miRNAs) are a class of small noncoding RNA (20-25 nucleotides) involved in gene regulation. In recent years, miRNAs have emerged as a key epigenetic mechanism in the development and physiology of the cardiovascular system. These molecular species regulate basic functions in virtually all cell types, and are therefore directly associated with the pathophysiology of a large number of cardiovascular diseases. Since their relatively recent discovery in extracellular fluids, miRNAs have been studied as potential biomarkers of disease. A wide array of studies have proposed miRNAs as circulating biomarkers of different cardiovascular pathologies (eg, myocardial infarction, coronary heart disease, and heart failure, among others), which may have superior physicochemical and biochemical properties than the conventional protein indicators currently used in clinical practice. In the present review, we provide a brief introduction to the field of miRNAs, paying special attention to their potential clinical application. This includes their possible role as new diagnostic or prognostic biomarkers in cardiovascular disease.
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Affiliation(s)
- David de Gonzalo-Calvo
- Grupo de Lípidos y Patología Cardiovascular, Instituto de Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.
| | | | - Vicenta Llorente-Cortés
- Grupo de Lípidos y Patología Cardiovascular, Instituto de Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Biomédicas de Barcelona (IibB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain
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Malik R, Mushtaque RS, Siddiqui UA, Younus A, Aziz MA, Humayun C, Mansoor K, Latif MA, Waheed S, Assad S, Khan I, Bukhari SM, DelCampo D, Adus A, Gannarapu S. Association Between Coronary Artery Disease and MicroRNA: Literature Review and Clinical Perspective. Cureus 2017; 9:e1188. [PMID: 28540143 PMCID: PMC5441689 DOI: 10.7759/cureus.1188] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Until recently, circulating micro-RNAs (miRNAs) have attracted major interest as novel biomarkers for the early diagnosis of coronary artery disease (CAD). This review article summarizes the available evidence on the correlation of micro-RNAs with both the clinical and subclinical coronary artery disease and highlights the necessity for exploring miRNAs as a potential diagnostic and prognostic biomarker of early CAD in an adult population. METHODS A systematic literature analysis and retrieval online systems Public/Publisher MEDLINE/ Excerpta Medica Database /Medical Literature Analysis and Retrieval System Online,(PUBMED/EMBASE/MEDLINE) search were conducted for relevant information. Search was limited to the articles published in English language and conducted on humans, January 2000 onwards. We excluded studies of heart surgery, coronary artery bypass grafting (CABG), angioplasty and heart transplant. Eighteen studies met the inclusion criteria. RESULTS Seven out of 18 studies were multivariate, i.e. adjusted for age, gender, body mass index (BMI), smoking, hypertension, diabetes, and blood lipid profiles, while the remaining twelve studies were univariate analysis. Different sources of miRNAs were used, i.e. plasma/serum, microparticles, whole blood, platelets, blood mononuclear intimal and endothelial progenitor cells were investigated. Fourteen out of 18 studies showed up-regulation of different miRNA in CAD patients and in vulnerable plaque disease. Four out of 18 studies showed both the up-regulation and down-regulation of miRNA in the population, while only three studies showed down-regulation of miRNA. Various sources and types of miRNA were used in each study. CONCLUSION This review gives an extensive overview of up-regulation and down-regulation of miRNA in CAD and non-CAD patients. The pattern of miRNA regulation with respect to CAD/non-CAD study subjects varies across individual studies and different parameters, which could be the possible reason for this aberrancy. We suggest further trials be conducted in future for highlighting the role of miRNA in CAD, which may improve both the diagnostic and therapeutic approaches to stratifying CAD burden in the general population.
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Affiliation(s)
- Rehan Malik
- Internal Medicine, Mount Sinai Medical Center, Miami Beach, Florida
| | - Raja S Mushtaque
- Center for Healthcare Advancement & Outcomes Research, Baptist Health Medical Group
| | - Usman A Siddiqui
- Center for Healthcare Advancement & Outcomes Research, Baptist Health Medical Group
| | - Adnan Younus
- Center for Healthcare Advancement & Outcomes Research, Baptist Health Medical Group
| | - Muhammad A Aziz
- Center for Healthcare Advancement & Outcomes Research, Baptist Health Medical Group
| | - Choudhry Humayun
- Center for Healthcare Advancement & Outcomes Research, Baptist Health Medical Group
| | - Kanaan Mansoor
- Center for Healthcare Advancement & Outcomes Research, Baptist Health Medical Group
| | - Muhammad A Latif
- Weiss Memorial Hospital, Internal Medicine, University of Illinois at Chicago
| | - Salman Waheed
- Cardiology-University of Kansas Hospital & Medical Center, University of Kansas Hospital & Medical Center
| | - Salman Assad
- Department of Medicine, Shifa Tameer-e-Millat University, Islamabad, Pakistan
| | - Idrees Khan
- Center for Healthcare Advancement & Outcomes Research, Baptist Health Medical Group
| | - Syed M Bukhari
- UPMC Mckeesport Internal Medicine Department, University of Pittsburgh Medical Center
| | - Daniel DelCampo
- Center for Healthcare Advancement & Outcomes Research, Baptist Health Medical Group
| | - Ali Adus
- Center for Healthcare Advancement & Outcomes Research, Baptist Health Medical Group
| | - Swetha Gannarapu
- Center for Healthcare Advancement & Outcomes Research, Baptist Health Medical Group
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Njock MS, Fish JE. Endothelial miRNAs as Cellular Messengers in Cardiometabolic Diseases. Trends Endocrinol Metab 2017; 28:237-246. [PMID: 27989505 DOI: 10.1016/j.tem.2016.11.009] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Revised: 11/21/2016] [Accepted: 11/23/2016] [Indexed: 01/08/2023]
Abstract
Metabolic syndrome is a clustering of risk factors that increases susceptibility to serious cardiometabolic complications, including type 2 diabetes (T2D) and myocardial infarction. Understanding the underlying mechanisms will advance the development of diagnostic and therapeutic approaches. A prominent feature of cardiometabolic diseases is endothelial dysfunction. Endothelial cell (EC) homeostasis and response to pathological stimuli are controlled by gene regulatory networks in which miRNAs play a critical role. Recently, miRNAs have been implicated as cell-cell messengers that can influence cellular function. This review investigates the known and potential roles for miRNA-based cell-cell communication in the control of cardiovascular health and explores the value of identifying miRNA biomarkers and developing therapeutics that harness or antagonize miRNA-based communication.
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Affiliation(s)
- Makon-Sébastien Njock
- Laboratory of Molecular Angiogenesis, GIGA-R, University of Liège, Liège, Belgium; Toronto General Hospital Research Institute, University Health Network, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, Toronto, Canada.
| | - Jason E Fish
- Toronto General Hospital Research Institute, University Health Network, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, Toronto, Canada.
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Faccini J, Ruidavets JB, Cordelier P, Martins F, Maoret JJ, Bongard V, Ferrières J, Roncalli J, Elbaz M, Vindis C. Circulating miR-155, miR-145 and let-7c as diagnostic biomarkers of the coronary artery disease. Sci Rep 2017; 7:42916. [PMID: 28205634 PMCID: PMC5311865 DOI: 10.1038/srep42916] [Citation(s) in RCA: 107] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Accepted: 01/17/2017] [Indexed: 12/14/2022] Open
Abstract
Coronary artery disease (CAD) is the most prevalent cause of mortality and morbidity worldwide and the number of individuals at risk is increasing. To better manage cardiovascular diseases, improved tools for risk prediction including the identification of novel accurate biomarkers are needed. MicroRNA (miRNA) are essential post-transcriptional modulators of gene expression leading to mRNA suppression or translational repression. Specific expression profiles of circulating miRNA have emerged as potential noninvasive diagnostic biomarkers of diseases. The aim of this study was to identify the potential diagnostic value of circulating miRNA with CAD. Circulating miR-145, miR-155, miR-92a and let-7c were selected and validated by quantitative PCR in 69 patients with CAD and 30 control subjects from the cross-sectional study GENES. The expression of miR-145, miR-155 and let-7c showed significantly reduced expression in patients with CAD compared to controls. Multivariate logistic regression analysis revealed that low levels of circulating let-7c, miR-145 and miR-155 were associated with CAD. Receiver operating curves analysis showed that let-7c, miR-145 or miR-155 were powerful markers for detecting CAD. Furthermore, we demonstrated that the combination of the three circulating miRNA managed to deliver a specific signature for diagnosing CAD.
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Affiliation(s)
- Julien Faccini
- INSERM UMR-1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.,Toulouse Paul Sabatier University, Toulouse, France
| | - Jean-Bernard Ruidavets
- Toulouse Paul Sabatier University, Toulouse, France.,CHU Toulouse, Department of Cardiology, Toulouse, France.,INSERM UMR-1027, Epidémiologie et Analyses en Santé publique, Toulouse, France
| | | | | | | | - Vanina Bongard
- Toulouse Paul Sabatier University, Toulouse, France.,CHU Toulouse, Department of Cardiology, Toulouse, France
| | - Jean Ferrières
- Toulouse Paul Sabatier University, Toulouse, France.,CHU Toulouse, Department of Cardiology, Toulouse, France.,INSERM UMR-1027, Epidémiologie et Analyses en Santé publique, Toulouse, France
| | | | - Meyer Elbaz
- INSERM UMR-1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.,Toulouse Paul Sabatier University, Toulouse, France.,CHU Toulouse, Department of Cardiology, Toulouse, France
| | - Cécile Vindis
- INSERM UMR-1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.,Toulouse Paul Sabatier University, Toulouse, France
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39
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The Emerging Role of MicroRNA-155 in Cardiovascular Diseases. BIOMED RESEARCH INTERNATIONAL 2016; 2016:9869208. [PMID: 28018919 PMCID: PMC5149600 DOI: 10.1155/2016/9869208] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Revised: 09/20/2016] [Accepted: 09/29/2016] [Indexed: 12/26/2022]
Abstract
MicroRNAs have been demonstrated to be involved in human diseases, including cardiovascular diseases. Growing evidences suggest that microRNA-155, a typical multifunctional microRNA, plays a crucial role in hematopoietic lineage differentiation, immunity, inflammation, viral infections, and vascular remodeling, which is linked to cardiovascular diseases such as coronary artery disease, abdominal aortic aneurysm, heart failure, and diabetic heart disease. The effects of microRNA-155 in different cell types through different target genes result in different mechanisms in diseases. MicroRNA-155 has been intensively studied in atherosclerosis and coronary artery disease. Contradictory results of microRNA-155 either promoting or preventing the pathophysiological process of atherosclerosis illustrate the complexity of this pleiotropic molecule. Therefore, more comprehensive studies of the underlying mechanisms of microRNA-155 involvement in cardiovascular diseases are required. Furthermore, a recent clinical trial of Miravirsen targeting microRNA-122 sheds light on exploiting microRNA-155 as a novel target to develop effective therapeutic strategies for cardiovascular diseases in the near future.
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40
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Busch A, Eken SM, Maegdefessel L. Prospective and therapeutic screening value of non-coding RNA as biomarkers in cardiovascular disease. ANNALS OF TRANSLATIONAL MEDICINE 2016; 4:236. [PMID: 27429962 DOI: 10.21037/atm.2016.06.06] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Non-coding RNA (ncRNA) is a class of genetic, epigenetic and translational regulators, containing short and long transcripts with intriguing abilities for use as biomarkers due to their superordinate role in disease development. In the past five years many of these have been investigated in cardiovascular diseases (CVD), mainly myocardial infarction (MI) and heart failure. To extend this view, we summarize the existing data about ncRNA as biomarker in the whole entity of CVDs by literature-based review and comparison of the identified candidates. The myomirs miRNA-1, -133a/b, -208a, -499 with well-defined cellular functions have proven equal to classic protein biomarkers for disease detection in MI. Other microRNAs (miRNAs) were reproducibly found to correlate with disease, disease severity and outcome in heart failure, stroke, coronary artery disease (CAD) and aortic aneurysm. An additional utilization has been discovered for therapeutic monitoring. The function of long non-coding transcripts is only about to be unraveled, yet shows great potential for outcome prediction. ncRNA biomarkers have a distinct role if no alternative test is available or has is performing poorly. With increasing mechanistic understanding, circulating miRNA and long non-coding transcripts will provide useful disease information with high predictive power.
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Affiliation(s)
- Albert Busch
- Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institute, Center for Molecular Medicine, Stockholm, Sweden
| | - Suzanne M Eken
- Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institute, Center for Molecular Medicine, Stockholm, Sweden
| | - Lars Maegdefessel
- Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institute, Center for Molecular Medicine, Stockholm, Sweden
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41
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Specific miRNA Disease Biomarkers in Blood, Serum and Plasma: Challenges and Prospects. Mol Diagn Ther 2016; 20:509-518. [DOI: 10.1007/s40291-016-0221-4] [Citation(s) in RCA: 147] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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42
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Navickas R, Gal D, Laucevičius A, Taparauskaitė A, Zdanytė M, Holvoet P. Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review. Cardiovasc Res 2016; 111:322-37. [PMID: 27357636 PMCID: PMC4996262 DOI: 10.1093/cvr/cvw174] [Citation(s) in RCA: 248] [Impact Index Per Article: 27.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Accepted: 05/19/2016] [Indexed: 12/31/2022] Open
Abstract
The aim of the present study is to identify microRNAs (miRs) with high potential to be used as biomarkers in plasma and/or serum to clinically diagnose, or provide accurate prognosis for survival in, patients with atherosclerosis, coronary artery disease, and acute coronary syndrome (ACS). A systematic search of published original research yielded a total of 72 studies. After review of the risk of bias of the published studies, according to Cochrane Collaboration and the QUADUAS Group standards, 19 studies were selected. Overall 52 different miRs were reported. In particular, miR-133a/b (5 studies), miR-208a/b (6 studies), and miR-499 (7 studies) were well studied and found to be significant diagnostic and/or prognostic markers across different cardiovascular disease progression stages. miR-1 and miR-145b are potential biomarkers of ACS; miR-1 with higher sensitivity for all acute myocardial infarction (AMI), and miR-145 for STEMI and worse outcome of AMI. But when miRs were studied across different ACS study populations, patients had varying degrees of coronary stenosis, which was identified as an important confounder that limited the ability to quantitatively pool the study results. The identified miRs were found to regulate endothelial function and angiogenesis (miR-1, miR-133), vascular smooth muscle cell differentiation (miR-133, miR-145), communication between vascular smooth muscle and endothelial cell to stabilize plaques (miR-145), apoptosis (miR-1, miR-133, miR-499), cardiac myocyte differentiation (miR-1, miR-133, miR-145, miR-208, miR-499), and to repress cardiac hypertrophy (miR-133). Their role in these processes may be explained by regulation of shared RNA targets such as cyclin-dependent kinase inhibitor 1A (or p21), ETS proto-oncogene 1, fascin actin-bundling protein 1, hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, insulin-like growth factor 1 receptor LIM and SH3 protein 1, purine nucleoside phosphorylase, and transgelin 2. These mechanistic data further support the clinical relevance of the identified miRs. miR-1, miR-133a/b, miR-145, miR-208a/b, and miR-499(a) in plasma and/or serum show some potential for diagnosis of cardiovascular disease. However, biased selection of miRs in most studies and unexplained contrasting results are major limitations of current miR research. Inconsistencies need to be addressed in order to definitively identify clinically useful miRs. Therefore, this paper presents important aspects to improve future miR research, including unbiased selection of miRs, standardization/normalization of reference miRs, adjustment for patient comorbidities and medication, and robust protocols of data-sharing plans that could prevent selective publication and selective reporting of miR research outcomes.
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Affiliation(s)
- Rokas Navickas
- Faculty of Medicine, Vilnius University, Vilnius, Lithuania Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania
| | - Diane Gal
- Department of Cardiovascular Sciences, Atherosclerosis and Metabolism Unit, KU Leuven, Leuven, Belgium
| | - Aleksandras Laucevičius
- Faculty of Medicine, Vilnius University, Vilnius, Lithuania Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania
| | | | | | - Paul Holvoet
- Department of Cardiovascular Sciences, Atherosclerosis and Metabolism Unit, KU Leuven, Leuven, Belgium
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Abstract
Atherosclerosis and its attendant clinical complications, such as myocardial infarction, stroke, and peripheral artery disease, are the leading cause of morbidity and mortality in Western societies. In response to biochemical and biomechanical stimuli, atherosclerotic lesion formation occurs from the participation of a range of cell types, inflammatory mediators, and shear stress. Over the past decade, microRNAs (miRNAs) have emerged as evolutionarily conserved, noncoding small RNAs that serve as important regulators and fine-tuners of a range of pathophysiological cellular effects and molecular signaling pathways involved in atherosclerosis. Accumulating studies reveal the importance of miRNAs in regulating key signaling and lipid homeostasis pathways that alter the balance of atherosclerotic plaque progression and regression. In this review, we highlight current paradigms of miRNA-mediated effects in atherosclerosis progression and regression. We provide an update on the potential use of miRNAs diagnostically for detecting increasing severity of coronary disease and clinical events. Finally, we provide a perspective on therapeutic opportunities and challenges for miRNA delivery in the field.
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Affiliation(s)
- Mark W Feinberg
- From the Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.W.F.); and Departments of Medicine and Cell Biology, Leon H Charney Division of Cardiology, New York University Medical Center (K.J.M.).
| | - Kathryn J Moore
- From the Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.W.F.); and Departments of Medicine and Cell Biology, Leon H Charney Division of Cardiology, New York University Medical Center (K.J.M.)
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Mazloom H, Alizadeh S, Pasalar P, Esfahani EN, Meshkani R. Downregulated microRNA-155 expression in peripheral blood mononuclear cells of type 2 diabetic patients is not correlated with increased inflammatory cytokine production. Cytokine 2015; 76:403-408. [DOI: 10.1016/j.cyto.2015.07.007] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2015] [Revised: 07/06/2015] [Accepted: 07/07/2015] [Indexed: 12/20/2022]
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45
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The role of microRNAs in coronary artery disease: From pathophysiology to diagnosis and treatment. Atherosclerosis 2015; 241:624-33. [PMID: 26117399 DOI: 10.1016/j.atherosclerosis.2015.06.037] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Revised: 05/31/2015] [Accepted: 06/17/2015] [Indexed: 01/08/2023]
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Schulte C, Zeller T. microRNA-based diagnostics and therapy in cardiovascular disease-Summing up the facts. Cardiovasc Diagn Ther 2015; 5:17-36. [PMID: 25774345 DOI: 10.3978/j.issn.2223-3652.2014.12.03] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Accepted: 12/10/2014] [Indexed: 12/21/2022]
Abstract
Circulating microRNAs (miRNAs) are discussed as potential disease-specific biomarkers in cardiovascular disease. Their diagnostic value has been examined in numerous studies and animal models with respect to coronary artery disease (CAD) and myocardial infarction (MI) and the prognostic abilities of circulating miRNAs in risk stratification of future disease have been evaluated. Various miRNAs are described to complement protein-based biomarkers or classical risk factors in the diagnosis of CAD or MI and even represent potential new biomarkers in the discrimination of unstable angina pectoris (UAP). Signatures consisting of sets of multiple miRNAs seem to improve the predictive power compared to single miRNAs. Furthermore, the emerging field of miRNA-based therapeutics has reached cardiovascular research. The first promising in vitro results are raising hope for future clinical application. However, methods and material used for RNA isolation, miRNA detection and normalization steps still lack ways of standardization and need to be considered carefully. This article reviews the current knowledge of miRNAs in cardiovascular disease focusing on CAD and MI and will provide an overview regarding the use of circulating miRNAs as biomarkers and potential therapeutic targets in the field of CAD.
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Affiliation(s)
- Christian Schulte
- 1 Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, 20246 Hamburg, Germany ; 2 German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Lübeck/Kiel, Hamburg, Germany
| | - Tanja Zeller
- 1 Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, 20246 Hamburg, Germany ; 2 German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Lübeck/Kiel, Hamburg, Germany
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