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Guo JY, Dong XY, Li S, Tang JF, Zhou CF. Chinese patent medicine: Opening new perspectives for treatment of post-endoscopic submucosal dissection esophageal stricture in esophageal cancer patients. World J Gastroenterol 2025; 31:102943. [PMID: 40248381 PMCID: PMC12001194 DOI: 10.3748/wjg.v31.i14.102943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 02/28/2025] [Accepted: 03/10/2025] [Indexed: 04/11/2025] Open
Abstract
Endoscopic submucosal dissection (ESD) is an effective technique for treating early esophageal cancer, and the prevention of postoperative esophageal stricture has emerged as a significant research topic. Zhou et al utilized an experimental minipig model to demonstrate that Kangfuxin (KFX) can improve postoperative esophageal stricture following ESD by inhibiting transforming growth factor-β1-driven fibrosis and the downstream fibrotic mediators Smad2/3. In this letter, we primarily discuss recent advancements in the treatment of esophageal stricture, the clinical applications of KFX, and the mechanisms involved in alleviating postoperative esophageal stricture, aiming to provide insights for advancing clinical practice and research in esophageal stricture after ESD.
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Affiliation(s)
- Jie-Yu Guo
- School of Life and Health Sciences, Institute of Biomedical Research, Wuhan 430068, Hubei Province, China
| | - Xue-Ying Dong
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, School of Life and Health Sciences, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, Hubei Province, China
| | - Shi Li
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, School of Life and Health Sciences, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, Hubei Province, China
| | - Jing-Feng Tang
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, School of Life and Health Sciences, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, Hubei Province, China
| | - Ce-Fan Zhou
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, School of Life and Health Sciences, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, Hubei Province, China
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Chen D, Wang X, Zhang S, Huang J, Li M, Wang L, Jiang T. The experimental study of the effect of fluid shear force on the migration rate of human umbilical vein endothelial cells. Biochem Biophys Res Commun 2025; 758:151619. [PMID: 40117976 DOI: 10.1016/j.bbrc.2025.151619] [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: 12/01/2024] [Revised: 03/04/2025] [Accepted: 03/10/2025] [Indexed: 03/23/2025]
Abstract
BACKGROUND The vascular endothelium is a continuous monolayer of flattened cells that cover the surface of the lumen of blood vessels. Endothelial cell damage can readily result in thrombus formation and thickening of the intima. Accelerating the migration and repair of peripheral endothelial cells is essential. Shear force is an important hydrodynamic factor affecting endothelial cell function. We aimed to investigate the effect of different shear forces on the migration rate of endothelial cells. METHODS Human umbilical vein endothelial cells (HUVECs) were used instead of endothelial cells to establish a cell scratch model. Plate flow chambers were then used to intervene in HUVECs growth with different shear force magnitudes (4 dyn/cm2, 8 dyn/cm2, and 12 dyn/cm2). The healing rate of the scratches was observed under light microscopy, and finally the expression of RhoA and CDC42 was detected by molecular experiments. The expression of CDC42 factor was inhibited by siRNA interference, and the wound healing ability of HUVECs in the control group and the CDC42 inhibition group under different fluid shear forces was observed under light microscopy. RESULTS High shear forces promote the healing of scratches. In addition, relatively strong shear forces promoted the expression of cytokines RhoA and CDC42. Compared with untransfected HUVECs, HUVECs with inhibition of CDC42 expression by siRNA interference showed weak migration ability in different fluid shear groups. CONCLUSION Increasing fluid shear force in a range (4-12 dyn/cm2) contributes to endothelial cell migration. Inhibition of CDC42 expression weakened the migration ability of HUVECs under different fluid shear forces.
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Affiliation(s)
- Dong Chen
- Dalian University of Technology, China; Department of Neurosurgery, Dalian University of Technology Affiliated Central Hospital, China; China Medical University, Shenyang, China
| | - Xianwei Wang
- Department of Neurosurgery, Dalian University of Technology Affiliated Central Hospital, China.
| | - Sen Zhang
- Department of Neurosurgery, Dalian University of Technology Affiliated Central Hospital, China; Dalian Medical University, Dalian, China
| | - Jiaming Huang
- Department of Neurosurgery, Dalian University of Technology Affiliated Central Hospital, China
| | - Mei Li
- Department of Neurosurgery, Dalian University of Technology Affiliated Central Hospital, China
| | | | - Tao Jiang
- Department of Neurosurgery, Dalian University of Technology Affiliated Central Hospital, China; China Medical University, Shenyang, China; West China Hospital, Sichuan University, Chengdu, China.
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Wei X, Wang L, Xing Z, Chen P, He X, Tuo X, Su H, Zhou G, Liu H, Fan Y. Glutamine synthetase accelerates re-endothelialization of vascular grafts by mitigating endothelial cell dysfunction in a rat model. Biomaterials 2025; 314:122877. [PMID: 39378796 DOI: 10.1016/j.biomaterials.2024.122877] [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: 02/07/2024] [Revised: 09/25/2024] [Accepted: 10/03/2024] [Indexed: 10/10/2024]
Abstract
Endothelial cell (EC) dysfunction within the aorta has long been recognized as a prominent contributor to the progression of atherosclerosis and the subsequent failure of vascular graft transplantation. However, the direct relationship between EC dysfunction and vascular remodeling remains to be investigated. In this study, we sought to address this knowledge gap by employing a strategy involving the release of glutamine synthetase (GS), which effectively activated endothelial metabolism and mitigates EC dysfunction. To achieve this, we developed GS-loaded small-diameter vascular grafts (GSVG) through the electrospinning technique, utilizing dual-component solutions consisting of photo-crosslinkable hyaluronic acid and polycaprolactone. Through an in vitro model of oxidized low-density lipoprotein-induced injury in human umbilical vein endothelial cells (HUVECs), we provided compelling evidence that the GSVG promoted the restoration of motility, angiogenic sprouting, and proliferation in dysfunctional HUVECs by enhancing cellular metabolism. Furthermore, the sequencing results indicated that these effects were mediated by miR-122-5p-related signaling pathways. Remarkably, the GSVG also exhibited regulatory capabilities in shifting vascular smooth muscle cells towards a contractile phenotype, mitigating inflammatory responses and thereby preventing vascular calcification. Finally, our data demonstrated that GS incorporation significantly enhanced re-endothelialization of vascular grafts in a ferric chloride-injured rat model. Collectively, our results offer insights into the promotion of re-endothelialization in vascular grafts by restoring dysfunctional ECs through the augmentation of cellular metabolism.
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Affiliation(s)
- Xinbo Wei
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, PR China
| | - Li Wang
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, PR China
| | - Zheng Xing
- School of Pharmacy, Changzhou University, Changzhou, 213164, PR China
| | - Peng Chen
- Department of Ultrasound, The Third Medical Center, Chinese PLA General Hospital, Beijing, PR China
| | - Xi He
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, PR China
| | - Xiaoye Tuo
- Department of Reparative and Reconstructive Surgery, 9 Jinyuanzhuang Rd., Peking University Shougang Hospital, PR China
| | - Haoran Su
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, PR China
| | - Gang Zhou
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, PR China
| | - Haifeng Liu
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, PR China.
| | - Yubo Fan
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, PR China.
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Raj B, Pg P, Sapa H, Shaji SS, T S, Kp AU, K K, Varma P. Small-Diameter Stents in Cardiovascular Applications. Chem Biodivers 2025:e202402008. [PMID: 39901606 DOI: 10.1002/cbdv.202402008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 02/01/2025] [Accepted: 02/03/2025] [Indexed: 02/05/2025]
Abstract
Small-diameter stents play a crucial role in treating congenital heart diseases and variety of vascular conditions that have application from paediatrics to geriatric conditions, and a comprehensive review in this direction is lacking. This review explores historical development, design innovations, material compositions and mechanistic insights into functions of small-diameter stents, with a specific emphasis on biodegradable options. The necessity for stents that can adapt to growth of paediatric patients is discussed, highlighting the transition from durable polymers to bioresorbable materials such as polylactic acid (PLA) and magnesium alloys. While acknowledging the advancements made in reducing complications like restenosis and thrombosis, the review addresses the challenges that persist, including the need for improved biocompatibility and minimization of late adverse cardiac events associated with certain stent technologies. A detailed examination of various stent generations emphasizes the importance of drug release kinetics, structural integrity and potential for personalized interventions based on patient-specific factors. The exploration of novel therapeutic compounds, including nanoparticles and interfering RNA, illustrates the ongoing research aimed at enhancing stent efficacy. Ultimately, the review seeks to provide a comprehensive understanding of current landscape while identifying the gaps that future research must address to develop the ideal stent for diverse patient populations.
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Affiliation(s)
- Bhavana Raj
- Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Institute of Medical Sciences and Research Centre, AIMS Health Sciences Campus, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Prajitha Pg
- Vel Tech Dr. Rangarajan Dr. Sagunthala R&D Institute of Science and Technology, (Veltech Dr. RR and Dr. SR. Technical University), Avadi, Chennai, India
- Kerala Law Academy Law College, Kerala Law Academy Law College Peroorkada, Thiruvananthapuram, Kerala, India
| | - Harika Sapa
- Department of Cardiovascular and Thoracic Surgery (C.V.T.S.), School of Medicine, Amrita Institute of Medical Sciences and Research Centre, AIMS Health Sciences Campus, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Shona Sara Shaji
- Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Institute of Medical Sciences and Research Centre, AIMS Health Sciences Campus, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Sreejith T
- Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Institute of Medical Sciences and Research Centre, AIMS Health Sciences Campus, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Althaf Umar Kp
- Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Institute of Medical Sciences and Research Centre, AIMS Health Sciences Campus, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Kaladhar K
- Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Institute of Medical Sciences and Research Centre, AIMS Health Sciences Campus, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Praveen Varma
- Department of Cardiovascular and Thoracic Surgery (C.V.T.S.), School of Medicine, Amrita Institute of Medical Sciences and Research Centre, AIMS Health Sciences Campus, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
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Chen J, Zhou C, Fang W, Yin J, Shi J, Ge J, Shen L, Liu SM, Liu SJ. Identification of endothelial protein C receptor as a novel druggable agonistic target for reendothelialization promotion and thrombosis prevention of eluting stent. Bioact Mater 2024; 41:485-498. [PMID: 39210965 PMCID: PMC11359769 DOI: 10.1016/j.bioactmat.2024.07.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 07/16/2024] [Accepted: 07/21/2024] [Indexed: 09/04/2024] Open
Abstract
The commercially available drug-eluting stent with limus (rapamycin, everolimus, etc.) or paclitaxel inhibits smooth muscle cell (SMC), reducing the in-stent restenosis, whereas damages endothelial cell (EC) and delays stent reendothelialization, increasing the risk of stent thrombosis (ST) and sudden cardiac death. Here we present a new strategy for promoting stent reendothelialization and preventing ST by exploring the application of precise molecular targets with EC specificity. Proteomics was used to investigate the molecular mechanism of EC injury caused by rapamycin. Endothelial protein C receptor (EPCR) was screened out as a crucial EC-specific effector. Limus and paclitaxel repressed the EPCR expression, while overexpression of EPCR protected EC from coating (eluting) drug-induced injury. Furthermore, the ligand activated protein C (APC), polypeptide TR47, and compound parmodulin 2, which activated the target EPCR, promoted EC functions and inhibited platelet or neutrophil adhesion, and enhanced rapamycin stent reendothelialization in the simulated stent environment and in vitro. In vivo, the APC/rapamycin-coating promoted reendothelialization rapidly and prevented ST more effectively than rapamycin-coating alone, in both traditional metal stents and biodegradable stents. Additionally, overexpression or activation of the target EPCR did not affect the cellular behavior of SMC or the inhibitory effect of rapamycin on SMC. In conclusion, EPCR is a promising therapeutical agonistic target for pro-reendothelialization and anti-thrombosis of eluting stent. Activation of EPCR protects against coating drugs-induced EC injury, inflammatory cell, or platelet adhesion onto the stent. The novel application formula for APC/rapamycin-combined eluting promotes stent reendothelialization and prevents ST.
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Affiliation(s)
- Jing Chen
- Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, PR China
- Department of Cardiology, The First Affliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510000, PR China
| | - Changyi Zhou
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China
- Research Unit of Cardiovascular Techniques and Devices, Chinese Academy of Medical Sciences, Fudan University, Shanghai, 200433, PR China
| | - Weilun Fang
- Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, PR China
| | - Jiasheng Yin
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China
- Research Unit of Cardiovascular Techniques and Devices, Chinese Academy of Medical Sciences, Fudan University, Shanghai, 200433, PR China
| | - Jian Shi
- Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, PR China
| | - Junbo Ge
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China
- Research Unit of Cardiovascular Techniques and Devices, Chinese Academy of Medical Sciences, Fudan University, Shanghai, 200433, PR China
| | - Li Shen
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China
- Research Unit of Cardiovascular Techniques and Devices, Chinese Academy of Medical Sciences, Fudan University, Shanghai, 200433, PR China
| | - Shi-Ming Liu
- Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, PR China
- Department of Cardiology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, PR China
| | - Shao-Jun Liu
- Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, PR China
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Ding Y, Warlick L, Chen M, Taddese E, Collins C, Fu R, Duan C, Wang X, Ware H, Sun C, Ameer G. 3D-printed, citrate-based bioresorbable vascular scaffolds for coronary artery angioplasty. Bioact Mater 2024; 38:195-206. [PMID: 38756202 PMCID: PMC11096684 DOI: 10.1016/j.bioactmat.2024.04.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 04/25/2024] [Accepted: 04/27/2024] [Indexed: 05/18/2024] Open
Abstract
Fully bioresorbable vascular scaffolds (BVSs) aim to overcome the limitations of metallic drug-eluting stents (DESs). However, polymer-based BVSs, such as Abbott's Absorb, the only US FDA-approved BVS, have had limited use due to increased strut thickness (157 μm for Absorb), exacerbated tissue inflammation, and increased risk of major cardiac events leading to inferior clinical performance when compared to metallic DESs. Herein we report the development of a drug-eluting BVS (DE-BVS) through the innovative use of a photopolymerizable, citrate-based biomaterial and a high-precision additive manufacturing process. BVS with a clinically relevant strut thickness of 62 μm can be produced in a high-throughput manner, i.e. one BVS per minute, and controlled release of the anti-restenosis drug everolimus can be achieved by engineering the structure of polymer coatings to fabricate drug-eluting BVS. We achieved the successful deployment of BVSs and DE-BVSs in swine coronary arteries using a custom-built balloon catheter and BVS delivery system and confirmed BVS safety and efficacy regarding maintenance of vessel patency for 28 days, observing an inflammation profile for BVS and DE-BVS that was comparable to the commercial XIENCE™ DES (Abbott Vascular).
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Affiliation(s)
- Yonghui Ding
- Centre for Advanced Regenerative Engineering (CARE), Northwestern University, Evanston, IL 60208, USA
- Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Liam Warlick
- Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Mian Chen
- Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Eden Taddese
- Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Caralyn Collins
- Centre for Advanced Regenerative Engineering (CARE), Northwestern University, Evanston, IL 60208, USA
- Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Rao Fu
- Centre for Advanced Regenerative Engineering (CARE), Northwestern University, Evanston, IL 60208, USA
- Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Chongwen Duan
- Centre for Advanced Regenerative Engineering (CARE), Northwestern University, Evanston, IL 60208, USA
- Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Xinlong Wang
- Centre for Advanced Regenerative Engineering (CARE), Northwestern University, Evanston, IL 60208, USA
- Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Henry Ware
- Centre for Advanced Regenerative Engineering (CARE), Northwestern University, Evanston, IL 60208, USA
- Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Cheng Sun
- Centre for Advanced Regenerative Engineering (CARE), Northwestern University, Evanston, IL 60208, USA
- Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Guillermo Ameer
- Centre for Advanced Regenerative Engineering (CARE), Northwestern University, Evanston, IL 60208, USA
- Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
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Yu H, Ahn J, Choi BG, Park S, Kang DO, Choi CU, Rha SW, Jeong MH. Three-Year Clinical Outcomes With the Cilotax Dual Drug-Eluting Stent vs Everolimus-Eluting Stents in Patients With Acute Myocardial Infarction. Tex Heart Inst J 2024; 51:e238271. [PMID: 38686684 PMCID: PMC11075153 DOI: 10.14503/thij-23-8271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2024]
Abstract
BACKGROUND This study compared the safety and effectiveness of paclitaxel/cilostazol-eluting Cilotax stents with those of everolimus-eluting stents in patients with acute myocardial infarction. Real-world data from the Korea Acute Myocardial Infarction Registry were examined. METHODS A total of 5,472 patients with acute myocardial infarction underwent percutaneous coronary intervention with Cilotax stents (n = 212) or everolimus-eluting stents (n = 5,260). The primary end point was the 3-year rate of target lesion failure. The other end points were major adverse cardiovascular events (a composite of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization), target vessel revascularization, and stent thrombosis. A propensity score matching analysis was performed to adjust for potential confounders by using a logistic regression model; propensity score matching generated 2 well-balanced groups (Cilotax group, n = 180; everolimus-eluting stents group, n = 170; N = 350). After propensity score matching, baseline clinical characteristics were similar between the groups. RESULTS After percutaneous coronary intervention, compared with the everolimus-eluting stents group, the Cilotax group more often had major adverse cardiovascular events (24.1% vs 18.5%; P = .042), myocardial infarction (8.0% vs 3.2%; P < .001), target lesion revascularization (8.0% vs 2.6%; P < .001), target vessel revascularization (11.3% vs 4.5%; P < .001), and stent thrombosis (4.7% vs 0.5%; P < .001) before matching. Even after matching, the Cilotax group had more frequent target lesion revascularization (9.4% vs 2.9%; P = .22) and stent thrombosis (5.6% vs 1.2%; P = .34). CONCLUSION In patients with acute myocardial infarction who underwent percutaneous coronary intervention, use of the Cilotax stent was associated with higher rates of target lesion revascularization, target vessel revascularization, and stent thrombosis than were everolimus-eluting stents. Use of the Cilotax dual drugeluting stent should be avoided in the treatment of myocardial infarction.
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Affiliation(s)
- HyeYon Yu
- School of Nursing, College of Medicine, Soonchunhyang University, Asan, Republic of Korea
| | - Jihun Ahn
- Department of Internal Medicine, Daejeon Eulji Medical Center, Eulji University College of Medicine, Daejeon, Republic of Korea
| | - Byoung Geol Choi
- Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Soohyung Park
- Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Dong Oh Kang
- Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Cheol Ung Choi
- Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Seung-Woon Rha
- Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Myung Ho Jeong
- Division of Cardiology, Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Republic of Korea
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Lungu CN, Creteanu A, Mehedinti MC. Endovascular Drug Delivery. Life (Basel) 2024; 14:451. [PMID: 38672722 PMCID: PMC11051410 DOI: 10.3390/life14040451] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 03/12/2024] [Accepted: 03/25/2024] [Indexed: 04/28/2024] Open
Abstract
Drug-eluting stents (DES) and balloons revolutionize atherosclerosis treatment by targeting hyperplastic tissue responses through effective local drug delivery strategies. This review examines approved and emerging endovascular devices, discussing drug release mechanisms and their impacts on arterial drug distribution. It emphasizes the crucial role of drug delivery in modern cardiovascular care and highlights how device technologies influence vascular behavior based on lesion morphology. The future holds promise for lesion-specific treatments, particularly in the superficial femoral artery, with recent CE-marked devices showing encouraging results. Exciting strategies and new patents focus on local drug delivery to prevent restenosis, shaping the future of interventional outcomes. In summary, as we navigate the ever-evolving landscape of cardiovascular intervention, it becomes increasingly evident that the future lies in tailoring treatments to the specific characteristics of each lesion. By leveraging cutting-edge technologies and harnessing the potential of localized drug delivery, we stand poised to usher in a new era of precision medicine in vascular intervention.
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Affiliation(s)
- Claudiu N. Lungu
- Department of Functional and Morphological Science, Faculty of Medicine and Pharmacy, Dunarea de Jos University, 800010 Galati, Romania;
| | - Andreea Creteanu
- Department of Pharmaceutical Technology, University of Medicine and Pharmacy Grigore T Popa, 700115 Iași, Romania
| | - Mihaela C. Mehedinti
- Department of Functional and Morphological Science, Faculty of Medicine and Pharmacy, Dunarea de Jos University, 800010 Galati, Romania;
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Yang Y, Yang Y, Hou Z, Wang T, Wu P, Shen L, Li P, Zhang K, Yang L, Sun S. Comprehensive review of materials, applications, and future innovations in biodegradable esophageal stents. Front Bioeng Biotechnol 2023; 11:1327517. [PMID: 38125305 PMCID: PMC10731276 DOI: 10.3389/fbioe.2023.1327517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 11/27/2023] [Indexed: 12/23/2023] Open
Abstract
Esophageal stricture (ES) results from benign and malignant conditions, such as uncontrolled gastroesophageal reflux disease (GERD) and esophageal neoplasms. Upper gastrointestinal endoscopy is the preferred diagnostic approach for ES and its underlying causes. Stent insertion using an endoscope is a prevalent method for alleviating or treating ES. Nevertheless, the widely used self-expandable metal stents (SEMS) and self-expandable plastic stents (SEPS) can result in complications such as migration and restenosis. Furthermore, they necessitate secondary extraction in cases of benign esophageal stricture (BES), rendering them unsatisfactory for clinical requirements. Over the past 3 decades, significant attention has been devoted to biodegradable materials, including synthetic polyester polymers and magnesium-based alloys, owing to their exceptional biocompatibility and biodegradability while addressing the challenges associated with recurring procedures after BES resolves. Novel esophageal stents have been developed and are undergoing experimental and clinical trials. Drug-eluting stents (DES) with drug-loading and drug-releasing capabilities are currently a research focal point, offering more efficient and precise ES treatments. Functional innovations have been investigated to optimize stent performance, including unidirectional drug-release and anti-migration features. Emerging manufacturing technologies such as three-dimensional (3D) printing and new biodegradable materials such as hydrogels have also contributed to the innovation of esophageal stents. The ultimate objective of the research and development of these materials is their clinical application in the treatment of ES and other benign conditions and the palliative treatment of malignant esophageal stricture (MES). This review aimed to offer a comprehensive overview of current biodegradable esophageal stent materials and their applications, highlight current research limitations and innovations, and offer insights into future development priorities and directions.
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Affiliation(s)
- Yaochen Yang
- Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, China
- Research Center for Biomedical Materials, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yuanyuan Yang
- Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhipeng Hou
- Research Center for Biomedical Materials, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, China
| | - Tingting Wang
- Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, China
| | - Peng Wu
- Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lufan Shen
- Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, China
| | - Peng Li
- Liaoning Research Institute for Eugenic Birth and Fertility, China Medical University, Shenyang, China
| | - Kai Zhang
- Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, China
| | - Liqun Yang
- Research Center for Biomedical Materials, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, China
- Liaoning Research Institute for Eugenic Birth and Fertility, China Medical University, Shenyang, China
| | - Siyu Sun
- Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, China
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10
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Park S, Rha SW, Choi BG, Kim W, Choi WG, Lee SJ, Lee JB, Park JY, Park SM, Jeong MH, Kim YH, Her AY, Kim MW, Chen KY, Kim BK, Shin ES, Seo JB, Ahn J, Choi SY, Byun JK, Cha JA, Hyun SJ, Choi CU, Park CG. Efficacy and safety of cilostazol-based triple antiplatelet therapy compared with clopidogrel-based dual antiplatelet therapy in patients with acute ST-elevation myocardial infarction undergoing percutaneous coronary intervention: A multicenter, randomized, open-label, phase 4 trial. Am Heart J 2023; 265:11-21. [PMID: 37406923 DOI: 10.1016/j.ahj.2023.06.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 06/27/2023] [Accepted: 06/28/2023] [Indexed: 07/07/2023]
Abstract
BACKGROUND Previous studies reported that compared to conventional dual antiplatelet therapy (DAT; aspirin + clopidogrel), triple antiplatelet therapy (TAT), involving the addition of cilostazol to DAT, had better clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). However, the optimal duration of TAT is yet to be determined. METHODS In total, 985 patients with STEMI who underwent primary percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) were prospectively enrolled in 15 PCI centers in South Korea and China. We randomly assigned patients into 3 groups: DAT (aspirin and clopidogrel for 12 months), TAT 1M (aspirin, clopidogrel, and cilostazol for 1 month), and TAT 6M (aspirin, clopidogrel, and cilostazol for 6 months). The primary endpoint was 1-year major adverse cardiovascular events (MACEs), defined as a composite of all-cause death, recurrent myocardial infarction, stroke, or repeat revascularization. RESULTS The primary endpoint did not differ among the 3 groups (8.8% in DAT, 11.0% in TAT 1M, and 11.6% in TAT 6M; hazard ratio for TAT 1M vs DAT, 1.302; 95% confidence interval [CI], 0.792-2.141; P = .297; hazard ratio for TAT 6M vs DAT, 1.358; 95% CI, 0.829-2.225; P = .225). With respect to in-hospital outcomes, more bleeding events occurred in the TAT group than in the DAT group (1.3% vs 4.7% vs 2.6%, P = .029), with no significant differences in major bleeding events. Additionally, the TAT group had a higher incidence of headaches (0% vs 1.6% vs 2.6%, P = .020). CONCLUSIONS The addition of cilostazol to DAT did not reduce the incidence of 1-year MACEs compared with DAT alone. Instead, it may be associated with an increased risk of drug intolerance and side effects, including in-hospital bleeding and headaches.
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Affiliation(s)
- Soohyung Park
- Cardiovascular Center, Korea University Guro Hospital, Seoul, South Korea
| | - Seung-Woon Rha
- Cardiovascular Center, Korea University Guro Hospital, Seoul, South Korea; Cardiovascular Research Institute, Korea University, Seoul, South Korea.
| | - Byoung Geol Choi
- Cardiovascular Center, Korea University Guro Hospital, Seoul, South Korea; Cardiovascular Research Institute, Korea University, Seoul, South Korea
| | - Woohyeun Kim
- Division of Cardiology, Department of Internal Medicine, Hanyang University Seoul Hospital, Seoul, South Korea
| | - Woong Gil Choi
- Cardiovascular Center, Chungbuk National University Hospital, Cheongju, South Korea
| | - Seung Jin Lee
- Division of Cardiology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, South Korea
| | - Jae Beom Lee
- Division of Cardiology, Department of Internal Medicine, Anyang SAM Hospital, Anyang, South Korea
| | - Ji Young Park
- Cardiovascular Center, Nowon Eulji Medical Center, Eulji University, Seoul, South Korea
| | - Sang Min Park
- Cardiovascular Center, Nowon Eulji Medical Center, Eulji University, Seoul, South Korea
| | - Myung Ho Jeong
- Heart Research Center, Chonnam National University Hospital and Medical School, Gwangju, South Korea
| | - Yong Hoon Kim
- Division of Cardiology, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Ae-Young Her
- Division of Cardiology, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Min Woong Kim
- Hanyang University Hanmaeum Changwon Hospital, Changwon, South Korea
| | - Kang-Yin Chen
- Cardiology Department, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Bae Keun Kim
- Department of Internal Medicine, Sungae Hospital, Seoul, South Korea
| | - Eun-Seok Shin
- Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Jae-Bin Seo
- Division of Cardiology, Department of Internal Medicine, Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea
| | - Jihun Ahn
- Department of Internal Medicine, Daejeon Eulji Medical Center, Eulji University, Daejeon, South Korea
| | - Se Yeon Choi
- Cardiovascular Research Institute, Korea University, Seoul, South Korea
| | - Jae Kyeong Byun
- Cardiovascular Research Institute, Korea University, Seoul, South Korea
| | - Jin Ah Cha
- Cardiovascular Research Institute, Korea University, Seoul, South Korea
| | - Su Jin Hyun
- Cardiovascular Research Institute, Korea University, Seoul, South Korea
| | - Cheol Ung Choi
- Cardiovascular Center, Korea University Guro Hospital, Seoul, South Korea
| | - Chang Gyu Park
- Cardiovascular Center, Korea University Guro Hospital, Seoul, South Korea
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11
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Kim S, Lee JS, Lee J, Kim YH, Kim JS, Lim SY, Kim SH, Ahn JC, Song WH. Fifteen-Year Nationwide Trend in Antiplatelet Treatment among Drug-Eluting Stent Recipients in Korea: Many Patients Receive Very Prolonged Dual-Antiplatelet Treatment, and Newer Drugs Are Replacing the Older Ones. J Clin Med 2023; 12:jcm12072675. [PMID: 37048759 PMCID: PMC10095404 DOI: 10.3390/jcm12072675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/21/2023] [Accepted: 03/31/2023] [Indexed: 04/07/2023] Open
Abstract
Drug-eluting stent (DES) recipients require 6–12 months of dual antiplatelet treatment (DAPT) and long-term aspirin mono-antiplatelet treatment (MAPT). Given the diversity of contemporary antiplatelet agents, antiplatelet treatment (APT) selection is becoming more complicated. We evaluated 15-year APT trends based on nationwide prescription data of 79,654 patients who underwent percutaneous coronary intervention (PCI) using DESs from 2002 to 2018 in Korea. DAPT (80.7%) was the most preferred initial APT post-PCI. Many DES recipients received prolonged DAPT (post-PCI 3 years: 41.0%; 10 years: 27.7%). There was a noticeable delay in DAPT-to-MAPT conversion from the mid to late 2000s (after the late-stent thrombosis concerns of first-generation DESs raised); the conversion after that was similar during the 2010s, occurring most robustly at 12–18 months post-PCI. Clopidogrel had long and increasingly been used for MAPT, surpassing aspirin. The recent increase in newer P2Y12 inhibitor prescriptions was noted. The patients treated with newer P2Y12 inhibitors were more likely younger men and presented with acute myocardial infarction. Real-world APT is evolving, and guideline–practice gaps exist. Further studies exploring the impact of diverse APT strategies on patient outcomes are expected to provide insights into optimal APT that can sophisticatedly balance the ischemic and bleeding risks.
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Affiliation(s)
- Sunwon Kim
- Cardiovascular Center, Korea University Ansan Hospital, Ansan-si 15355, Republic of Korea
| | - Jong-Seok Lee
- Cardiovascular Center, Korea University Ansan Hospital, Ansan-si 15355, Republic of Korea
| | - Jungkuk Lee
- Hanmi Pharmaceuticals, Songpa-gu, Seoul 05545, Republic of Korea
| | - Yong-Hyun Kim
- Cardiovascular Center, Korea University Ansan Hospital, Ansan-si 15355, Republic of Korea
| | - Jin-Seok Kim
- Cardiovascular Center, Korea University Ansan Hospital, Ansan-si 15355, Republic of Korea
| | - Sang-Yup Lim
- Cardiovascular Center, Korea University Ansan Hospital, Ansan-si 15355, Republic of Korea
| | - Seong Hwan Kim
- Cardiovascular Center, Korea University Ansan Hospital, Ansan-si 15355, Republic of Korea
| | - Jeong-Cheon Ahn
- Cardiovascular Center, Korea University Ansan Hospital, Ansan-si 15355, Republic of Korea
| | - Woo-Hyuk Song
- Cardiovascular Center, Korea University Ansan Hospital, Ansan-si 15355, Republic of Korea
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12
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Wei L, Gao Z. Recent research advances on corrosion mechanism and protection, and novel coating materials of magnesium alloys: a review. RSC Adv 2023; 13:8427-8463. [PMID: 36926015 PMCID: PMC10013130 DOI: 10.1039/d2ra07829e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 03/01/2023] [Indexed: 03/17/2023] Open
Abstract
Magnesium alloys have achieved a good balance between biocompatibility and mechanical properties, and have great potential for clinical application, and their performance as implant materials has been continuously improved in recent years. However, a high degradation rate of Mg alloys in a physiological environment remains a major limitation before clinical application. In this review, according to the human body's intake of elements, the current mainstream implanted magnesium alloy system is classified and discussed, and the corrosion mechanism of magnesium alloy in vivo and in vitro is described, including general corrosion, localized corrosion, pitting corrosion, and degradation of body fluid environment impact etc. The introduction of methods to improve the mechanical properties and biocorrosion resistance of magnesium alloys is divided into two parts: the alloying part mainly discusses the strengthening mechanisms of alloying elements, including grain refinement strengthening, solid solution strengthening, dislocation strengthening and precipitation strengthening etc.; the surface modification part introduces the ideas and applications of novel materials with excellent properties such as graphene and biomimetic materials in the development of functional coatings. Finally, the existing problems are summarized, and the future development direction is prospected.
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Affiliation(s)
- Liangyu Wei
- School of Material Science and Engineering, University of Science and Technology Beijing Beijing 100083 China
| | - Ziyuan Gao
- Central Research Institute of Building and Construction (CRIBC) Beijing 100088 China +86 18969880147
- State Key Laboratory of Iron and Steel Industry Environmental Protection Beijing 100088 China
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13
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Zhang J, Duan Y, Yu H, Jing L, Li Y, Jia X, Jin D, Liu H. Effects of TCFA on stent neointimal coverage at 9 months after EXCEL drug-eluting stent implantation assessed by OCT. Herz 2023; 48:64-71. [PMID: 34981128 DOI: 10.1007/s00059-021-05095-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 10/11/2021] [Accepted: 11/30/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND The aim of this study was to investigate the effects of thin-cap fibroatheromas (TCFAs) on stent neointimal coverage at the 9‑month follow-up after EXCEL stent implantation assessed by optical coherence tomography (OCT). METHODS A total of 93 patients with non-ST elevation acute coronary syndrome (NSTEACS) who underwent EXCEL stent implantation were prospectively enrolled in the study and divided into a TCFA group (n = 47) and a non-TCFA group (n = 46) according to whether EXCEL stents covered the TCFAs. A TCFA was defined as a plaque with lipid content in more than one quadrant and fibrous cap thickness measuring less than 65 μm. The effect of TCFAs on stent neointimal coverage at the 9‑month follow-up after stent implantation was evaluated by OCT. The primary study endpoints were the incidence of neointimal uncoverage and stent malapposition. RESULTS At the 9‑month follow-up, the minimal lumen diameter of the TCFA group tended to be smaller (2.8 ± 0.8 vs. 2.1 ± 0.8, p = 0.08) and the diameter of stenosis in the TCFA group tended to be larger (15.1 ± 10.3% vs. 26.3 ± 15.1%, p = 0.08) than those in the non-TCFA group. The mean intimal thickness of the TCFA group was significantly lower than that of the non-TCFA group (67.2 ± 35.5 vs. 145.1 ± 48.7, p < 0.001). The uncovered struts (10.1 ± 9.7 vs. 4.8 ± 4.3, p = 0.05) and malapposed struts (2.1 ± 4.7 vs. 0.3 ± 0.5, p = 0.003) in the TCFA group were more significant than those in the non-TCFA group. Multivariate analysis showed that TCFAs and lesion types were independent predictors of incomplete neointimal coverage (p < 0.05), and lesion types were independent predictors of stent malapposition (p < 0.05). CONCLUSION In patients with NSTEACS, TCFAs delayed endothelium coverage at 9 months after stent implantation, and TCFAs were independent predictors of incomplete neointimal coverage of the stent.
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Affiliation(s)
- Jiao Zhang
- Department of Cardiology, Beijing Electric Power Hospital, State Grid Corporation, Beijing, China.,Department of Cardiology, The Third Medical Center of Chinese PLA General Hospital, No.69 Yongding Road, Haidian District, 100089, Beijing, China
| | - Yuanyuan Duan
- Department of Geriatrics, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Hong Yu
- Department of Cardiology, Beijing Electric Power Hospital, State Grid Corporation, Beijing, China
| | - Limin Jing
- Department of Cardiology, Beijing Electric Power Hospital, State Grid Corporation, Beijing, China
| | - Yi Li
- Department of Cardiology, The Third Medical Center of Chinese PLA General Hospital, No.69 Yongding Road, Haidian District, 100089, Beijing, China
| | - Xiaowei Jia
- Department of Cardiology, The Third Medical Center of Chinese PLA General Hospital, No.69 Yongding Road, Haidian District, 100089, Beijing, China
| | - Dekui Jin
- Department of Cardiology, The Third Medical Center of Chinese PLA General Hospital, No.69 Yongding Road, Haidian District, 100089, Beijing, China
| | - Huiliang Liu
- Department of Cardiology, Beijing Electric Power Hospital, State Grid Corporation, Beijing, China. .,Department of Cardiology, The Third Medical Center of Chinese PLA General Hospital, No.69 Yongding Road, Haidian District, 100089, Beijing, China.
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14
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Lakalayeh GA, Rahvar M, Nazeri N, Ghanbari H. Evaluation of drug-eluting nanoparticle coating on magnesium alloy for development of next generation bioabsorbable cardiovascular stents. Med Eng Phys 2022; 108:103878. [DOI: 10.1016/j.medengphy.2022.103878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 07/28/2022] [Accepted: 08/22/2022] [Indexed: 10/15/2022]
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Outcomes and prognostic factors of patients treated for in-stent restenosis: a retrospective single-center experience. Egypt Heart J 2022; 74:42. [PMID: 35596845 PMCID: PMC9124276 DOI: 10.1186/s43044-022-00281-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 05/12/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The incidence of in-stent restenosis (ISR) remains relatively common despite the use of drug-eluting stents. Outcomes and prognostic factors following ISR revascularization are still being investigated. We aimed to describe the outcomes following different ISR treatment strategies in order to identify prognostic factors associated with worse outcomes. RESULTS In a retrospective cohort study, we included patients who were admitted to our department and treated for ISR, from January 2017 to December 2018. All patients were followed up for a median period of 24 months. Major cardiac adverse event (MACE) was a composite outcome of the following events: myocardial infarction, target vessel revascularization, target lesion revascularization or cardiovascular death. MACEs were collected during follow-up. Our population consisted of 116 patients. Mean age was 60 years old with a sex ratio of 2.8. During follow-up, 44 patients (37.9%) had at least one MACE. Independent factors identified by multivariate logistic regression were ISR of the proximal left anterior descending artery [Odds ratio (OR) = 1.29; 95% confidence interval (95% CI) 1.16-1.81; p = 0.05], diffuse ISR [OR = 2.16; 95% CI 1.1-3.47; p = 0.022], double or triple vessel disease [OR = 2.97; 95% CI 1.2-6.8; p = 0.008], two or more stents per lesion [OR = 1.82; 95% CI 1.14-2.21, p = 0.031] and absence of post-dilatation in the initial angioplasty [OR = 1.32; 95% CI 1-1.35; p = 0.04]. CONCLUSIONS Our study suggested that ISR is related to poor outcomes. Identifying prognostic factors would play a key role in the refinement of interventional techniques.
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16
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Kim C, Lee SG, Lim S, Jung M, Kwon SP, Hong J, Kang M, Sohn HS, Go S, Moon S, Lee SJ, Kim JS, Kim BS. A Senolytic-Eluting Coronary Stent for the Prevention of In-Stent Restenosis. ACS Biomater Sci Eng 2022; 8:1921-1929. [PMID: 35416659 DOI: 10.1021/acsbiomaterials.1c01611] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The vast majority of drug-eluting stents (DES) elute either sirolimus or one of its analogues. While limus drugs stymie vascular smooth muscle cell (VSMC) proliferation to prevent in-stent restenosis, their antiproliferative nature is indiscriminate and limits healing of the endothelium in stented vessels, increasing the risk of late-stent thrombosis. Oxidative stress, which is associated with vascular injury from stent implantation, can induce VSMCs to undergo senescence, and senescent VSMCs can produce pro-inflammatory cytokines capable of inducing proliferation of neighboring nonsenescent VSMCs. We explored the potential of senolytic therapy, which involves the selective elimination of senescent cells, in the form of a senolytic-eluting stent (SES) for interventional cardiology. Oxidative stress was modeled in vitro by exposing VSMCs to H2O2, and H2O2-mediated senescence was evaluated by cytochemical staining of senescence-associated β-galactosidase activity and qRT-PCR. Quiescent VSMCs were then treated with the conditioned medium (CM) of H2O2-treated VSMCs. Proliferative effects of CM were analyzed by staining for proliferating cell nuclear antigen. Senolytic effects of the first-generation senolytic ABT263 were observed in vitro, and the effects of ABT263 on endothelial cells were also investigated through an in vitro re-endothelialization assay. SESs were prepared by dip coating. Iliofemoral arteries of hypercholesteremic rabbits were implanted with SES, everolimus-eluting stents (EESs), or bare-metal stents (BMSs), and the area of stenosis was measured 4 weeks post-implantation using optical coherence tomography. We found that a portion of H2O2-treated VSMCs underwent senescence, and that CM of H2O2-treated senescent VSMCs triggered the proliferation of quiescent VSMCs. ABT263 reverted H2O2-mediated senescence and the proliferative capacity of senescent VSMC CM. Unlike everolimus, ABT263 did not affect endothelial cell migration and/or proliferation. SES, but not EES, significantly reduced stenosis area in vivo compared with bare-metal stents (BMSs). This study shows the potential of SES as an alternative to current forms of DES.
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Affiliation(s)
- Cheesue Kim
- School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea
| | - Seul-Gee Lee
- Yonsei Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Songhyun Lim
- School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea
| | - Mungyo Jung
- School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea
| | - Sung Pil Kwon
- School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea
| | - Jihye Hong
- Interdisciplinary Program for Bioengineering, Seoul National University, Seoul 08826, Republic of Korea
| | - Mikyung Kang
- Interdisciplinary Program for Bioengineering, Seoul National University, Seoul 08826, Republic of Korea
| | - Hee Su Sohn
- School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea
| | - Seokhyeong Go
- Interdisciplinary Program for Bioengineering, Seoul National University, Seoul 08826, Republic of Korea
| | - Sangjun Moon
- School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea
| | - Seung-Jun Lee
- Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Jung-Sun Kim
- Yonsei Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.,Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Byung-Soo Kim
- School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea.,Interdisciplinary Program for Bioengineering, Seoul National University, Seoul 08826, Republic of Korea.,Institute of Chemical Processes, Institute of Engineering Research, and BioMAX, Seoul National University, Seoul 08826, Republic of Korea
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17
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Lee SJ, Choi DW, Suh Y, Hong SJ, Ahn CM, Kim JS, Kim BK, Ko YG, Choi D, Park EC, Jang Y, Nam CM, Hong MK. Long-Term Clinical Outcomes Between Biodegradable and Durable Polymer Drug-Eluting Stents: A Nationwide Cohort Study. Front Cardiovasc Med 2022; 9:873114. [PMID: 35571196 PMCID: PMC9098972 DOI: 10.3389/fcvm.2022.873114] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 04/12/2022] [Indexed: 11/13/2022] Open
Abstract
Background Despite the theoretical benefits of biodegradable polymer drug-eluting stents (BP-DES), clinical benefits of BP-DES over durable polymer DES (DP-DES) have not been clearly demonstrated. Using data from a large-volume nationwide cohort, we compared long-term clinical outcomes between BP-DES- and DP-DES-treated patients. Methods A retrospective cohort study that enrolled all patients who underwent percutaneous coronary intervention (PCI) with new-generation DES between 2010 and 2016 in Korea was conducted by using the National Health Insurance Service database. The outcomes of interest were all-cause death, cardiovascular death, and myocardial infarction (MI). Results A total of 127,731 patients treated with new-generation DES with thin struts (<90 μm) were enrolled for this analysis. After stabilized inverse probability of treatment weighting, the incidence of all-cause death was significantly lower in patients treated with BP-DES (n = 19,521) at 5 years after PCI (11.3 vs. 13.0% in those treated with DP-DES [n = 108,067], hazard ratio [HR] 0.92, 95% confidence interval [CI], 0.88–0.96, p < 0.001), while showing no statistically significant difference at 2 years after PCI (5.7 vs. 6.0%, respectively, HR 0.95, 95% CI, 0.89–1.01, p = 0.238). Similarly, use of BP-DES was associated with a lower incidence of cardiovascular death (7.4 vs. 9.6% in those treated with DP-DES, HR 0.82, 95% CI, 0.77–0.87, p < 0.001), and MI (7.4 vs. 8.7%, respectively, HR 0.90, 95% CI, 0.86–0.94, p = 0.006) at 5 years after PCI. There was no statistically significant difference of cardiovascular death (4.6 vs. 4.9%, respectively, HR 0.93, 95% CI, 0.85–1.01, p = 0.120) and MI (5.0 vs. 5.1%, respectively, HR 0.98, 95% CI, 0.92–1.05, p = 0.461) at 2 years after PCI. Conclusions Implantation of BP-DES was associated with a lower risk of all-cause death, cardiovascular death, and MI compared with DP-DES implantation. This difference was clearly apparent at 5 years after DES implantation. Clinical Trial Registration ClinicalTrial.gov, NCT04715594.
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Affiliation(s)
- Seung-Jun Lee
- Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Dong-Woo Choi
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Cancer Big Data Center, National Cancer Control Institute, National Cancer Center, Goyang, South Korea
| | - Yongsung Suh
- Myongji Hospital, Hanyang University College of Medicine, Goyang, South Korea
| | - Sung-Jin Hong
- Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Chul-Min Ahn
- Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jung-Sun Kim
- Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Byeong-Keuk Kim
- Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Young-Guk Ko
- Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Donghoon Choi
- Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Eun-Cheol Park
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Yangsoo Jang
- Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Chung-Mo Nam
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Chung-Mo Nam
| | - Myeong-Ki Hong
- Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
- *Correspondence: Myeong-Ki Hong
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Shah P, Chandra S. Review on emergence of nanomaterial coatings in bio-engineered cardiovascular stents. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103224] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Clare J, Ganly J, Bursill CA, Sumer H, Kingshott P, de Haan JB. The Mechanisms of Restenosis and Relevance to Next Generation Stent Design. Biomolecules 2022; 12:biom12030430. [PMID: 35327622 PMCID: PMC8945897 DOI: 10.3390/biom12030430] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/07/2022] [Accepted: 03/08/2022] [Indexed: 02/04/2023] Open
Abstract
Stents are lifesaving mechanical devices that re-establish essential blood flow to the coronary circulation after significant vessel occlusion due to coronary vessel disease or thrombolytic blockade. Improvements in stent surface engineering over the last 20 years have seen significant reductions in complications arising due to restenosis and thrombosis. However, under certain conditions such as diabetes mellitus (DM), the incidence of stent-mediated complications remains 2–4-fold higher than seen in non-diabetic patients. The stents with the largest market share are designed to target the mechanisms behind neointimal hyperplasia (NIH) through anti-proliferative drugs that prevent the formation of a neointima by halting the cell cycle of vascular smooth muscle cells (VSMCs). Thrombosis is treated through dual anti-platelet therapy (DAPT), which is the continual use of aspirin and a P2Y12 inhibitor for 6–12 months. While the most common stents currently in use are reasonably effective at treating these complications, there is still significant room for improvement. Recently, inflammation and redox stress have been identified as major contributing factors that increase the risk of stent-related complications following percutaneous coronary intervention (PCI). The aim of this review is to examine the mechanisms behind inflammation and redox stress through the lens of PCI and its complications and to establish whether tailored targeting of these key mechanistic pathways offers improved outcomes for patients, particularly those where stent placement remains vulnerable to complications. In summary, our review highlights the most recent and promising research being undertaken in understanding the mechanisms of redox biology and inflammation in the context of stent design. We emphasize the benefits of a targeted mechanistic approach to decrease all-cause mortality, even in patients with diabetes.
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Affiliation(s)
- Jessie Clare
- Department of Chemistry and Biotechnology, Swinburne University of Technology, Melbourne, VIC 3122, Australia; (J.C.); (J.G.); (P.K.)
- Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia
| | - Justin Ganly
- Department of Chemistry and Biotechnology, Swinburne University of Technology, Melbourne, VIC 3122, Australia; (J.C.); (J.G.); (P.K.)
- Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia
| | - Christina A. Bursill
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5000, Australia;
- Vascular Research Centre, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia
- ARC Centre of Excellence for Nanoscale BioPhotonics, Adelaide, SA 5000, Australia
| | - Huseyin Sumer
- Department of Chemistry and Biotechnology, Swinburne University of Technology, Melbourne, VIC 3122, Australia; (J.C.); (J.G.); (P.K.)
- Correspondence: (H.S.); (J.B.d.H.)
| | - Peter Kingshott
- Department of Chemistry and Biotechnology, Swinburne University of Technology, Melbourne, VIC 3122, Australia; (J.C.); (J.G.); (P.K.)
- ARC Training Centre in Surface Engineering for Advanced Materials (SEAM), Swinburne University of Technology, Melbourne, VIC 3122, Australia
| | - Judy B. de Haan
- Department of Chemistry and Biotechnology, Swinburne University of Technology, Melbourne, VIC 3122, Australia; (J.C.); (J.G.); (P.K.)
- Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia
- Department Cardiometabolic Health, University of Melbourne, Melbourne, VIC 3010, Australia
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
- Correspondence: (H.S.); (J.B.d.H.)
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20
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Fiuza C, Polak-Kraśna K, Antonini L, Petrini L, Carroll O, Ronan W, Vaughan TJ. An experimental investigation into the physical, thermal and mechanical degradation of a polymeric bioresorbable scaffold. J Mech Behav Biomed Mater 2021; 125:104955. [PMID: 34749206 DOI: 10.1016/j.jmbbm.2021.104955] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 10/22/2021] [Accepted: 11/01/2021] [Indexed: 12/01/2022]
Abstract
This study presents a comprehensive evaluation of the mechanical, micro-mechanical and physical properties of Reva Medical Fantom Encore Bioresorbable Scaffolds (BRS) subjected to a thermally-accelerated degradation protocol. The Fantom Encore BRS were immersed in phosphate buffered saline solution at 50 °C for 112 days with radial compression testing, nanoindentation, differential scanning calorimetry, gel permeation chromatography and mass loss characterisation performed at consecutive time points. In the initial stages of degradation (Days 0-21), the Fantom Encore BRS showed increases in radial strength and stiffness, despite a substantial reduction in in molecular weight, with a slight increase in the melt temperature also observed. In the second phase (Days 35-54), the radial strength of the BRS samples were maintained despite a continued loss in molecular weight. However, during this phase, the ductility of the stent showed a reduction, with stent fracture occurring earlier in the crimp process and with lower amounts of plastic deformation evident under visual examination post-fracture. In the final phase (Days 63-112), the load-bearing capacity of the Fantom Encore BRS showed continued reduction, with decreases in radial stiffness and strength, and drastic reduction in the work-to-fracture of the devices. Throughout each phase, there was a steady increase in the relative crystallinity, with limited mass loss until day 112 and only minor changes in glass transition and melt temperatures. Limited changes were observed in nano-mechanical properties, with measured local elastic moduli and hardness values remaining largely similar throughout degradation. Given that the thermally-accelerated in vitro conditions represented a four-fold acceleration of physiological conditions, these results suggest that the BRS scaffolds could exhibit substantially brittle behaviour after ∼ one year of implantation.
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Affiliation(s)
- Constantino Fiuza
- Biomechanics Research Centre (BioMEC), Biomedical Engineering, School of Engineering, College of Science and Engineering, National University of Ireland Galway, Galway, Ireland
| | - Katarzyna Polak-Kraśna
- Biomechanics Research Centre (BioMEC), Biomedical Engineering, School of Engineering, College of Science and Engineering, National University of Ireland Galway, Galway, Ireland
| | - Luca Antonini
- Laboratory of Biological Structure Mechanics, Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Milano, Italy
| | - Lorenza Petrini
- Department of Civil and Environmental Engineering, Politecnico di Milano, Milano, Italy
| | - Oliver Carroll
- CÚRAM, Centre for Research in Medical Devices, Biomedical Sciences, National University of Ireland Galway, Galway, Ireland
| | - William Ronan
- Biomechanics Research Centre (BioMEC), Biomedical Engineering, School of Engineering, College of Science and Engineering, National University of Ireland Galway, Galway, Ireland
| | - Ted J Vaughan
- Biomechanics Research Centre (BioMEC), Biomedical Engineering, School of Engineering, College of Science and Engineering, National University of Ireland Galway, Galway, Ireland.
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21
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Chakraborty R, Chatterjee P, Dave JM, Ostriker AC, Greif DM, Rzucidlo EM, Martin KA. Targeting smooth muscle cell phenotypic switching in vascular disease. JVS Vasc Sci 2021; 2:79-94. [PMID: 34617061 PMCID: PMC8489222 DOI: 10.1016/j.jvssci.2021.04.001] [Citation(s) in RCA: 98] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 04/01/2021] [Indexed: 12/26/2022] Open
Abstract
Objective The phenotypic plasticity of vascular smooth muscle cells (VSMCs) is central to vessel growth and remodeling, but also contributes to cardiovascular pathologies. New technologies including fate mapping, single cell transcriptomics, and genetic and pharmacologic inhibitors have provided fundamental new insights into the biology of VSMC. The goal of this review is to summarize the mechanisms underlying VSMC phenotypic modulation and how these might be targeted for therapeutic benefit. Methods We summarize findings from extensive literature searches to highlight recent discoveries in the mechanisms underlying VSMC phenotypic switching with particular relevance to intimal hyperplasia. PubMed was searched for publications between January 2001 and December 2020. Search terms included VSMCs, restenosis, intimal hyperplasia, phenotypic switching or modulation, and drug-eluting stents. We sought to highlight druggable pathways as well as recent landmark studies in phenotypic modulation. Results Lineage tracing methods have determined that a small number of mature VSMCs dedifferentiate to give rise to oligoclonal lesions in intimal hyperplasia and atherosclerosis. In atherosclerosis and aneurysm, single cell transcriptomics reveal a striking diversity of phenotypes that can arise from these VSMCs. Mechanistic studies continue to identify new pathways that influence VSMC phenotypic plasticity. We review the mechanisms by which the current drug-eluting stent agents prevent restenosis and note remaining challenges in peripheral and diabetic revascularization for which new approaches would be beneficial. We summarize findings on new epigenetic (DNA methylation/TET methylcytosine dioxygenase 2, histone deacetylation, bromodomain proteins), transcriptional (Hippo/Yes-associated protein, peroxisome proliferator-activity receptor-gamma, Notch), and β3-integrin-mediated mechanisms that influence VSMC phenotypic modulation. Pharmacologic and genetic targeting of these pathways with agents including ascorbic acid, histone deacetylase or bromodomain inhibitors, thiazolidinediones, and integrin inhibitors suggests potential therapeutic value in the setting of intimal hyperplasia. Conclusions Understanding the molecular mechanisms that underlie the remarkable plasticity of VSMCs may lead to novel approaches to treat and prevent cardiovascular disease and restenosis.
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Affiliation(s)
- Raja Chakraborty
- Department of Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Conn.,Department of Pharmacology, Yale University School of Medicine, New Haven, Conn
| | - Payel Chatterjee
- Department of Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Conn.,Department of Pharmacology, Yale University School of Medicine, New Haven, Conn
| | - Jui M Dave
- Department of Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Conn.,Department of Genetics, Yale University School of Medicine, New Haven, Conn
| | - Allison C Ostriker
- Department of Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Conn.,Department of Pharmacology, Yale University School of Medicine, New Haven, Conn
| | - Daniel M Greif
- Department of Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Conn.,Department of Genetics, Yale University School of Medicine, New Haven, Conn
| | - Eva M Rzucidlo
- Department Surgery, Section of Vascular Surgery, McLeod Regional Medical Center, Florence, SC
| | - Kathleen A Martin
- Department of Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Conn.,Department of Pharmacology, Yale University School of Medicine, New Haven, Conn
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22
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Luo J, Gao Y, Liu Y, Huang X, Zhang DX, Cao H, Jing T, Liu F, Li B. Self-Assembled Degradable Nanogels Provide Foliar Affinity and Pinning for Pesticide Delivery by Flexibility and Adhesiveness Adjustment. ACS NANO 2021; 15:14598-14609. [PMID: 34427447 DOI: 10.1021/acsnano.1c04317] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/18/2023]
Abstract
At present, it is highly important to develop a simple and compatible nano delivery system for pesticides for foliar application, which can improve their insecticidal efficacy and resistance to adverse climates while reducing the environmental risks. Polyethylene glycol and 4,4-methylenediphenyl diisocyanate are used as hydrophilic soft and hydrophobic hard segments, respectively, for polymer self-assembly and polyurethane gelation in a nanoreactor. The nanocarrier synthesis and the pesticide loading are realized by a one-step integration procedure and suited well for hydrophobic active compounds. Modifying the molecular structure of the soft segment can adjust the flexibility of the nanocarriers and result in viscosity and deformation characteristics. After foliar spray application, the foliar flattening state of the nanogels increases the foliar protection area by 2.21 times and improves both pesticide exposure area and target contact efficiency. Concurrently, the flexibility and viscosity of the nanogels increase the washing resistance and the retention rate of the pesticide by approximately 80 times under continuous washing. The encapsulation of the nanogels reduces the foliar ultraviolet (UV) degradation and aquatic pesticide exposure, which increase the security of λ-cyhalothrine by 9.33 times. Moreover, the degradability of nanogels is beneficial for pesticide exposure and reducing pollution. This system has simple preparation, good properties, and environmental friendliness, making the nanocarriers promising for delivering pesticides.
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Affiliation(s)
- Jian Luo
- College of Plant Protection, Shandong Agricultural University, Tai'an, Shandong 271018, P.R. China
| | - Yue Gao
- College of Plant Protection, Shandong Agricultural University, Tai'an, Shandong 271018, P.R. China
| | - Yukun Liu
- College of Plant Protection, Shandong Agricultural University, Tai'an, Shandong 271018, P.R. China
| | - Xueping Huang
- College of Plant Protection, Shandong Agricultural University, Tai'an, Shandong 271018, P.R. China
| | - Da-Xia Zhang
- Department of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, P.R. China
| | - Haichao Cao
- College of Plant Protection, Shandong Agricultural University, Tai'an, Shandong 271018, P.R. China
| | - Tongfang Jing
- College of Plant Protection, Shandong Agricultural University, Tai'an, Shandong 271018, P.R. China
| | - Feng Liu
- College of Plant Protection, Shandong Agricultural University, Tai'an, Shandong 271018, P.R. China
| | - Beixing Li
- College of Plant Protection, Shandong Agricultural University, Tai'an, Shandong 271018, P.R. China
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23
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Milder DA, Kam PC. Perioperative implications of newer generation drug-eluting coronary stents: A narrative review. Anaesth Intensive Care 2021; 49:338-348. [PMID: 34134534 DOI: 10.1177/0310057x20984792] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Newer generation drug-eluting stents are the most commonly inserted stent in the setting of percutaneous coronary intervention. This narrative review focuses on the evidence underpinning the perioperative management of patients with newer generation drug-eluting stents undergoing non-cardiac surgery. Six studies reported the incidence of major adverse cardiovascular events according to the time interval from percutaneous coronary intervention to non-cardiac surgery, and the comparative risks of newer and first generation drug-eluting stents. No study demonstrated an increased risk of major adverse cardiovascular events once three months had elapsed between stent implantation and non-cardiac surgery. Only one study included patients with third and fourth generation drug-eluting stents. Seven studies analysed the relationship between antiplatelet therapy, major adverse cardiovascular events and perioperative bleeding. The risks of major adverse cardiovascular events do not appear to be increased if antiplatelet therapy is ceased for less than seven days but are increased if it is discontinued for more than seven days. Most studies reported no differences in the incidence of major bleeding associated with antiplatelet therapy. The risk of perioperative major adverse cardiovascular events in non-cardiac surgery does not appear to be increased after three months following implantation with newer generation drug-eluting stents. However, the possibility of increased risk cannot be excluded as most studies were inadequately powered. The thrombotic risk is substantially reduced in patients with fourth (polymer free) generation drug-eluting stents, and urgent non-cardiac surgery can be considered one month after percutaneous coronary intervention. Larger multicentre studies are needed to define the optimal window for non-cardiac surgery after percutaneous coronary intervention and provide definitive perioperative strategies for patients presenting for non-cardiac surgery after the implantation of newer generation drug-eluting stents.
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Affiliation(s)
- David A Milder
- Department of Anaesthesia, Concord Repatriation General Hospital, Concord, Australia
| | - Peter Ca Kam
- Department of Anaesthetics, Royal Prince Alfred Hospital, Camperdown, Australia.,Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia
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24
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Cherian AM, Nair SV, Maniyal V, Menon D. Surface engineering at the nanoscale: A way forward to improve coronary stent efficacy. APL Bioeng 2021; 5:021508. [PMID: 34104846 PMCID: PMC8172248 DOI: 10.1063/5.0037298] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 04/26/2021] [Indexed: 12/12/2022] Open
Abstract
Coronary in-stent restenosis and late stent thrombosis are the two major inadequacies of vascular stents that limit its long-term efficacy. Although restenosis has been successfully inhibited through the use of the current clinical drug-eluting stent which releases antiproliferative drugs, problems of late-stent thrombosis remain a concern due to polymer hypersensitivity and delayed re-endothelialization. Thus, the field of coronary stenting demands devices having enhanced compatibility and effectiveness to endothelial cells. Nanotechnology allows for efficient modulation of surface roughness, chemistry, feature size, and drug/biologics loading, to attain the desired biological response. Hence, surface topographical modification at the nanoscale is a plausible strategy to improve stent performance by utilizing novel design schemes that incorporate nanofeatures via the use of nanostructures, particles, or fibers, with or without the use of drugs/biologics. The main intent of this review is to deliberate on the impact of nanotechnology approaches for stent design and development and the recent advancements in this field on vascular stent performance.
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Affiliation(s)
- Aleena Mary Cherian
- Amrita Centre for Nanosciences and Molecular Medicine, Amrita
Vishwa Vidyapeetham, Ponekkara P.O. Cochin 682041, Kerala,
India
| | - Shantikumar V. Nair
- Amrita Centre for Nanosciences and Molecular Medicine, Amrita
Vishwa Vidyapeetham, Ponekkara P.O. Cochin 682041, Kerala,
India
| | - Vijayakumar Maniyal
- Department of Cardiology, Amrita Institute of Medical Science
and Research Centre, Amrita Vishwa Vidyapeetham, Ponekkara P.O. Cochin
682041, Kerala, India
| | - Deepthy Menon
- Amrita Centre for Nanosciences and Molecular Medicine, Amrita
Vishwa Vidyapeetham, Ponekkara P.O. Cochin 682041, Kerala,
India
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25
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Zhang WJ, Qiao X, Guo WF, Liang XY, Li Y, Wang ZL. Duration of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome Treated With New Generation Stents: A Meta-Analysis of Randomized Controlled Trials. Front Cardiovasc Med 2021; 8:615396. [PMID: 33614748 PMCID: PMC7886789 DOI: 10.3389/fcvm.2021.615396] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 01/12/2021] [Indexed: 11/13/2022] Open
Abstract
Background and Objective: The optimum duration of dual antiplatelet therapy (DAPT) remains uncertain in patients with acute coronary syndrome treated with new generation stents. This meta-analysis was performed to investigate ischemia and bleeding outcomes with different DAPT strategies. Methods: PubMed, Embase, Cochrane and Web of science from inception to May 27, 2020, were systematically searched. Randomized controlled trials were included to compare short-term (6 months or less) with standard (12 months) DAPT in patients with acute coronary syndrome treated with new generation stents. The primary endpoints were myocardial infarction, definite or probable stent thrombosis and major bleeding. The secondary endpoints included all-cause death, cardiovascular death, stroke, target vessel revascularization and net adverse clinical events. Random effect model and fixed effect model were used to calculate the odds ratio (OR) and 95% confidence interval (CI) of each endpoint. Results: Four randomized controlled trials and seven subgroup analyses of larger randomized controlled trials, including a total of 21,344 patients with acute coronary syndrome, met our inclusion criteria. The shorter DAPT was associated with significantly lower major bleeding compared with the standard DAPT (OR 0.71, 95% CI 0.56–0.90, P = 0.005, I2 = 25%), while without increasing the risk of myocardial infarction (OR 1.18, 0.88–1.58, P = 0.28, I2 = 20%), definite or probable stent thrombosis (OR 1.60, 0.98–2.59, P = 0.06, I2 = 0%). No significantly difference was observed in the risk of all-cause death (OR 0.96, 0.72–1.27, P = 0.76, I2 = 2%), cardiovascular death (OR 0.91, 0.62–1.33, P = 0.62, I2 = 0%), stroke (OR 0.84, 0.54–1.30, P = 0.43, I2 = 0%), target vessel revascularization (OR 1.14, 0.84–1.55, P = 0.41, I2 = 8%), and net adverse clinical events (OR 0.93, 0.80–1.07, P = 0.3, I2 = 18%) between the two groups. Conclusions: In patients with acute coronary syndrome treated with new generation stents, the shorter DAPT leads to a marked reduction in the risk of major bleeding compared with the standard DAPT. This benefit is achieved without increasing the risk of mortality or ischemic outcomes. The study protocol was registered in PROSPERO (CRD42020189871).
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Affiliation(s)
- Wen-Jiao Zhang
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Xuan Qiao
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Wen-Fen Guo
- Department of Cardiology, Baiyin Third People's Hospital, Baiyin, China
| | - Xi-Ying Liang
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Yan Li
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Zhi-Lu Wang
- Department of Cardiology, The First Hospital of Lanzhou University, Lanzhou, China
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26
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Schulz C, Krüger-Genge A, Lendlein A, Küpper JH, Jung F. Potential Effects of Nonadherent on Adherent Human Umbilical Venous Endothelial Cells in Cell Culture. Int J Mol Sci 2021; 22:ijms22031493. [PMID: 33540846 PMCID: PMC7867347 DOI: 10.3390/ijms22031493] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/25/2021] [Accepted: 01/27/2021] [Indexed: 12/20/2022] Open
Abstract
The adherence and shear-resistance of human umbilical venous endothelial cells (HUVEC) on polymers is determined in vitro in order to qualify cardiovascular implant materials. In these tests, variable fractions of HUVEC do not adhere to the material but remain suspended in the culture medium. Nonadherent HUVEC usually stop growing, rapidly lose their viability and can release mediators able to influence the growth and function of the adherent HUVEC. The aim of this study was the investigation of the time dependent behaviour of HUVEC under controlled nonadherent conditions, in order to gain insights into potential influences of these cells on their surrounding environment in particular adherent HUVEC in the context of in vitro biofunctionality assessment of cardiovascular implant materials. Data from adherent or nonadherent HUVEC growing on polystyrene-based cell adhesive tissue culture plates (TCP) or nonadhesive low attachment plates (LAP) allow to calculate the number of mediators released into the culture medium either from adherent or nonadherent cells. Thus, the source of the inflammatory mediators can be identified. For nonadherent HUVEC, a time-dependent aggregation without further proliferation was observed. The rate of apoptotic/dead HUVEC progressively increased over 90% within two days. Concomitant with distinct blebbing and loss of membrane integrity over time, augmented releases of prostacyclin (PGI2, up to 2.91 ± 0.62 fg/cell) and platelet-derived growth factor BB (PDGF-BB, up to 1.46 ± 0.42 fg/cell) were detected. The study revealed that nonadherent, dying HUVEC released mediators, which can influence the surrounding microenvironment and thereby the results of in vitro biofunctionality assessment of cardiovascular implant materials. Neglecting nonadherent HUVEC bears the risk for under- or overestimation of the materials endothelialization potential, which could lead to the loss of relevant candidates or to uncertainty with regard to their suitability for cardiac applications. One approach to minimize the influence from nonadherent endothelial cells could be their removal shortly after observing initial cell adhesion. However, this would require an individual adaptation of the study design, depending on the properties of the biomaterial used.
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Affiliation(s)
- Christian Schulz
- Fraunhofer Project Group PZ-Syn of the Fraunhofer Institute for Cell Therapy and Immunology, Branch Bioanalytics and Bioprocesses (IZI-BB), 14476 Potsdam-Golm, Germany, Institute of Biotechnology, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Brandenburg, Germany;
- Institute of Active Polymers and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, 14513 Teltow, Germany; (A.K.-G.); (F.J.)
| | - Anne Krüger-Genge
- Institute of Active Polymers and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, 14513 Teltow, Germany; (A.K.-G.); (F.J.)
- Department of Anesthesia, Pain Management and Perioperative Medicine, Faculty of Medicine, Dalhousie University, Halifax, NS 6299, Canada
| | - Andreas Lendlein
- Institute of Active Polymers and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, 14513 Teltow, Germany; (A.K.-G.); (F.J.)
- Institute of Chemistry, University of Potsdam, Karl-Liebknecht-Straße 24-25, 14469 Potsdam, Germany
- Correspondence:
| | - Jan-Heiner Küpper
- Institute of Biotechnology, Molecular Cell Biology, Brandenburg University of Technology, 01968 Senftenberg, Germany;
| | - Friedrich Jung
- Institute of Active Polymers and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, 14513 Teltow, Germany; (A.K.-G.); (F.J.)
- Institute of Biotechnology, Molecular Cell Biology, Brandenburg University of Technology, 01968 Senftenberg, Germany;
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27
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Nezami FR, Athanasiou LS, Edelman ER. Endovascular drug-delivery and drug-elution systems. BIOMECHANICS OF CORONARY ATHEROSCLEROTIC PLAQUE 2021:595-631. [DOI: 10.1016/b978-0-12-817195-0.00028-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
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28
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Li G, Zhao M, Xu F, Yang B, Li X, Meng X, Teng L, Sun F, Li Y. Synthesis and Biological Application of Polylactic Acid. Molecules 2020; 25:E5023. [PMID: 33138232 PMCID: PMC7662581 DOI: 10.3390/molecules25215023] [Citation(s) in RCA: 149] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 10/19/2020] [Accepted: 10/24/2020] [Indexed: 12/12/2022] Open
Abstract
Over the past few decades, with the development of science and technology, the field of biomedicine has rapidly developed, especially with respect to biomedical materials. Low toxicity and good biocompatibility have always been key targets in the development and application of biomedical materials. As a degradable and environmentally friendly polymer, polylactic acid, also known as polylactide, is favored by researchers and has been used as a commercial material in various studies. Lactic acid, as a synthetic raw material of polylactic acid, can only be obtained by sugar fermentation. Good biocompatibility and biodegradability have led it to be approved by the U.S. Food and Drug Administration (FDA) as a biomedical material. Polylactic acid has good physical properties, and its modification can optimize its properties to a certain extent. Polylactic acid blocks and blends play significant roles in drug delivery, implants, and tissue engineering to great effect. This article describes the synthesis of polylactic acid (PLA) and its raw materials, physical properties, degradation, modification, and applications in the field of biomedicine. It aims to contribute to the important knowledge and development of PLA in biomedical applications.
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Affiliation(s)
| | | | | | | | | | | | | | - Fengying Sun
- School of Life Sciences, Jilin University, Changchun 130012, China; (G.L.); (M.Z.); (F.X.); (B.Y.); (X.L.); (X.M.); (L.T.)
| | - Youxin Li
- School of Life Sciences, Jilin University, Changchun 130012, China; (G.L.); (M.Z.); (F.X.); (B.Y.); (X.L.); (X.M.); (L.T.)
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29
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Zhang DM, Chen S. In-Stent Restenosis and a Drug-Coated Balloon: Insights from a Clinical Therapeutic Strategy on Coronary Artery Diseases. Cardiol Res Pract 2020; 2020:8104939. [PMID: 33163230 PMCID: PMC7605950 DOI: 10.1155/2020/8104939] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 09/29/2020] [Accepted: 10/10/2020] [Indexed: 12/14/2022] Open
Abstract
Coronary heart disease is a major cause of death and disability in developed countries. Stent implantation has become an efficacious treatment for a culprit lesion vessel of the coronary artery. However, 10%-20% restenosis is still an important complication that restricts the clinical safety and efficacy of drug-eluting stents. In-stent restenosis may lead to the recurrence of major cardiovascular adverse events, including angina pectoris, acute myocardial infarction, and even sudden cardiac death. These events are currently serious problems that occur after coronary stent implantation. Clinical physicians face a difficult choice for in-stent restenosis treatment. Recent studies indicate that a drug-coated balloon has promising clinical efficacy similar to the drug-eluting stents for treating coronary in-stent restenosis. Therefore, in this study, we highlight the progress of coronary intervention and the use of drug-coated balloons in the treatment of in-stent restenosis (ISR).
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Affiliation(s)
- Dai-Min Zhang
- Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, China
| | - Shaoliang Chen
- Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, China
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Zhang B, Yao R, Hu C, Maitz MF, Wu H, Liu K, Yang L, Luo R, Wang Y. Epigallocatechin gallate mediated sandwich-like coating for mimicking endothelium with sustained therapeutic nitric oxide generation and heparin release. Biomaterials 2020; 269:120418. [PMID: 33143876 DOI: 10.1016/j.biomaterials.2020.120418] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 09/15/2020] [Accepted: 09/20/2020] [Indexed: 12/22/2022]
Abstract
In-stent restenosis after stenting is generally characterized by an inflammatory response, excessive proliferation of smooth muscle cells, and delayed healing of the endothelium layer. In this study, inspired by catechol/gallol surface chemistry, a sandwich-like layer-by-layer (LBL) coating was developed using chitosan and heparin as polyelectrolytes, along with the embedding of an epigallocatechin gallate/copper (EGCG/Cu) complex. The embedding of EGCG stabilized the coating by various intermolecular interactions in the LBL coating (e.g., π-π stacking, weak intermolecular crosslinking, and enriched hydrogen bonding) and supported the sustained release of the cargo heparin over 90 days. This design enabled a biomimetic endothelium function in terms of the sustained release of heparin and continuous in situ generation of nitric oxide, driven by the catalytic decomposition of endogenous S-nitrostothiols by copper ions. The result showed enhanced durability of anticoagulation and suppressed inflammatory response. Moreover, the "sandwich-like" coating supported the growth of endothelial cells and up-regulated the protein expression of vascular endothelial growth factor, while effectively suppressing the proliferation and migration of smooth muscle cells (SMCs) via the up-regulation of cyclic guanosine monophosphate. Ex vivo and in vivo experiments demonstrated the effectiveness of the sandwich-like coating in preventing thrombosis formation, suppressing the growth of SMCs, reducing the infiltration and activation of inflammatory cells, and ultimately achieving rapid in situ endothelialization. Hence, the EGCG-assisted sandwich-like coating might be used as a robust and versatile surface modification strategy for implantable cardiovascular devices.
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Affiliation(s)
- Bo Zhang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China
| | - Ruijuan Yao
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China
| | - Cheng Hu
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China
| | - Manfred F Maitz
- Max Bergmann Center of Biomaterials, Leibniz Institute of Polymer Research Dresden, Dresden, 01069, Germany; Key Lab. for Advanced Technologies of Materials, Ministry of Education, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China
| | - Haoshuang Wu
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China
| | - Kunpeng Liu
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China
| | - Li Yang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China
| | - Rifang Luo
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China.
| | - Yunbing Wang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China.
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Jang WJ, Chun WJ, Park IH, Choi KH, Song YB, Koo BK, Doh JH, Hong SJ, Nam CW, Gwon HC. Impact of stent designs of second-generation drug-eluting stents on long-term outcomes in coronary bifurcation lesions. Catheter Cardiovasc Interv 2020; 98:458-467. [PMID: 32729655 DOI: 10.1002/ccd.29137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 06/02/2020] [Accepted: 06/27/2020] [Indexed: 11/08/2022]
Abstract
OBJECTIVES We compared the long-term clinical outcomes of four different types of second-generation drug-eluting stents (DESs) in coronary bifurcation lesions. BACKGROUND Clinical outcomes of different designs of second-generation DESs are not well known in bifurcation lesions. METHODS Patients who underwent percutaneous coronary intervention with second-generation DESs for coronary bifurcation lesion were enrolled from 21 centers in South Korea. A total of 2,526 patients was evaluated and divided into four treatment groups according to DES type: bioabsorbable polymer biolimus-eluting stent (BP-BES group, n = 514), platinum chromium everolimus-eluting stent (PtCr-EES group, n = 473), cobalt nickel zotarolimus-eluting stent (CoNi-ZES group, n = 736), or cobalt chromium everolimus-eluting stent (CoCr-EES group, n = 803). Primary outcome was target lesion failure (TLF, defined as a composite of cardiac death, target vessel myocardial infarction, or target lesion revascularization). Inverse probability of treatment weighting (IPTW) was performed to reduce selection bias and potential confounding factors. RESULTS For 5 years of follow-up, the rates of TLF among the four DES groups were not significantly different (6.2% for BP-BES group, 8.2% for PtCr-EES group, 6.5% for CoNi-ZES group, and 8.6% for CoCr-EES group, p = .434). The results were consistent after IPTW adjustment (6.8, 8.4, 6.0, and 7.5%, respectively, p = .554). In subgroup analysis, the similarity of long-term outcomes among the four different types of second-generation DES was consistent across subgroups regardless of side branch treatment (p for interaction = .691). CONCLUSION There seems to be no significant difference in long-term clinical outcomes among patients who received different types of second-generation DES for coronary bifurcation lesion.
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Affiliation(s)
- Woo Jin Jang
- Division of Cardiology, Department of Internal Medicine, Seoul Hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea
| | - Woo Jung Chun
- Division of Cardiology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea
| | - Ik Hyun Park
- Division of Cardiology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea
| | - Ki Hong Choi
- Division of Cardiology, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young Bin Song
- Division of Cardiology, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Bon-Kwon Koo
- Division of Cardiology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Joon-Hyung Doh
- Division of Cardiology, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea
| | - Soon-Jun Hong
- Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Republic of Korea
| | - Chang-Wook Nam
- Division of Cardiology, Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, Republic of Korea
| | - Hyeon-Cheol Gwon
- Division of Cardiology, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Wu Z, Xu C, You W, Ye F, Wu X. Outcomes in Patients Fully Covered With Coronary Artery Aneurysm and Stenosis Lesion by Second Generation Drug-Eluting Stents After 1 Year. Angiology 2020; 71:942-947. [PMID: 32720510 DOI: 10.1177/0003319720944346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
We evaluated the safety and efficacy of second-generation drug-eluting stents (DES) fully covering a coronary artery aneurysm (CAA) and stenosis lesion. Patients (n = 33) with CAA and stenosis lesion (>60%) were enrolled between January 2014 and December 2017. Baseline characteristics and biochemical variables were recorded during hospital admission. Changes in CAA resolution (the reduction on CAA size), minimal lumen diameter (MLD), and diameter stenosis (DS) were determined before, just after, and 1 year after percutaneous coronary intervention (PCI). After DES implantation, MLD and DS after PCI were improved compared with those before PCI (P < .01). Also, thrombolysis in myocardial infarction blood flow was significantly enhanced after PCI (P < .01). One year after PCI, maximal CAA diameter in patients with CAA and stenosis lesion was significantly reduced compared with those just after PCI (P < .01). Meanwhile, CAA resolution ratio in these patients were more than those just after PCI (P < .01). Furthermore, there was a significant reduction about CAA length in these patients (P < .01). Last, there were no clinical events (including cardiac death, myocardial infarction, and revascularization) in the study. Second-generation DES implantation fully covering CAA and stenosis lesion was safe and effective.
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Affiliation(s)
- Zhiming Wu
- Department of Cardiology, 385685Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Chen Xu
- Department of Cardiology, 385685Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Wei You
- Department of Cardiology, 385685Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Fei Ye
- Department of Cardiology, 385685Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Xiangqi Wu
- Department of Cardiology, 385685Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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Hamideh RA, Akbari B, Fathi P, Misra SK, Sutrisno A, Lam F, Pan D. Biodegradable MRI Visible Drug Eluting Stent Reinforced by Metal Organic Frameworks. Adv Healthc Mater 2020; 9:e2000136. [PMID: 32548977 DOI: 10.1002/adhm.202000136] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 04/13/2020] [Indexed: 12/18/2022]
Abstract
Metal-organic frameworks (MOFs) have applications in numerous fields. However, the development of MOF-based "theranostic" macroscale devices is not achieved. Here, heparin-coated biocompatible MOF/poly(ε-caprolactone) (PCL) "theranostic" stents are developed, where NH2 -Materials of Institute Lavoisier (MIL)-101(Fe) encapsulates and releases rapamycin (an immunosuppressive drug). These stents also act as a remarkable source of contrast in ex vivo magnetic resonance imaging (MRI) compared to the invisible polymeric stent. The in vitro release patterns of heparin and rapamycin respectively can ensure a type of programmed model to prevent blood coagulation immediately after stent placement in the artery and stenosis over a longer term. Due to the presence of hydrolysable functionalities in MOFs, the stents are shown to be highly biodegradable in degradation tests under various conditions. Furthermore, there is no compromise of mechanical strength or flexibility with MOF compositing. The system described here promises many biomedical applications in macroscale theranostic devices. The use of MOF@PCL can render a medical device MRI-visible while simultaneously acting as a carrier for therapeutic agents.
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Affiliation(s)
- Rezvani Alanagh Hamideh
- Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, P.O. Box 14395-1561, Tehran, Iran
- Department of Bioengineering, Beckman Institute of Advanced Science and Technology, Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Carle Foundation Hospital, 611 West Park Street, Urbana, IL, 61801, USA
| | - Babak Akbari
- Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, P.O. Box 14395-1561, Tehran, Iran
| | - Parinaz Fathi
- Department of Bioengineering, Beckman Institute of Advanced Science and Technology, Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Carle Foundation Hospital, 611 West Park Street, Urbana, IL, 61801, USA
| | - Santosh K Misra
- Department of Bioengineering, Beckman Institute of Advanced Science and Technology, Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Carle Foundation Hospital, 611 West Park Street, Urbana, IL, 61801, USA
| | - Andre Sutrisno
- NMR/EPR Laboratory, School of Chemical Sciences, University of Illinois at Urbana-Champaign, IL, USA
| | - Fan Lam
- Department of Bioengineering, Beckman Institute of Advanced Science and Technology, Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Carle Foundation Hospital, 611 West Park Street, Urbana, IL, 61801, USA
| | - Dipanjan Pan
- Department of Bioengineering, Beckman Institute of Advanced Science and Technology, Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Carle Foundation Hospital, 611 West Park Street, Urbana, IL, 61801, USA
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland Baltimore, Health Sciences Facility III, 670 W Baltimore St., Baltimore, MD, 21201, USA
- Department of Pediatrics, University of Maryland Baltimore, Health Sciences Facility III, 670 W Baltimore St., Baltimore, MD, 21201, USA
- Department of Chemical, Biochemical and Environmental Engineering, University of Maryland Baltimore County, Interdisciplinary Health Sciences Facility, 1000 Hilltop Circle, Baltimore, MD, 21250, USA
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Bonora M, Wieckowski MR, Sinclair DA, Kroemer G, Pinton P, Galluzzi L. Targeting mitochondria for cardiovascular disorders: therapeutic potential and obstacles. Nat Rev Cardiol 2019; 16:33-55. [PMID: 30177752 DOI: 10.1038/s41569-018-0074-0] [Citation(s) in RCA: 209] [Impact Index Per Article: 34.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
A large body of evidence indicates that mitochondrial dysfunction has a major role in the pathogenesis of multiple cardiovascular disorders. Over the past 2 decades, extraordinary efforts have been focused on the development of agents that specifically target mitochondria for the treatment of cardiovascular disease. Despite such an intensive wave of investigation, no drugs specifically conceived to modulate mitochondrial functions are currently available for the clinical management of cardiovascular disease. In this Review, we discuss the therapeutic potential of targeting mitochondria in patients with cardiovascular disease, examine the obstacles that have restrained the development of mitochondria-targeting agents thus far, and identify strategies that might empower the full clinical potential of this approach.
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Affiliation(s)
- Massimo Bonora
- Ruth L. and David S. Gottesman Institute for Stem Cell, Regenerative Medicine Research, Department of Cell Biology and Stem Cell Institute, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Mariusz R Wieckowski
- Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland
| | - David A Sinclair
- Department of Genetics, Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA, USA.,Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, Australia
| | - Guido Kroemer
- Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.,INSERM, U1138, Paris, France.,Université Paris Descartes/Paris V, Paris, France.,Université Pierre et Marie Curie, Paris, France.,Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France.,Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.,Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden
| | - Paolo Pinton
- Department of Morphology, Surgery, and Experimental Medicine, Section of Pathology, Oncology, and Experimental Biology, Laboratory for Technologies of Advanced Therapies, University of Ferrara, Ferrara, Italy. .,Maria Cecilia Hospital, GVM Care & Research, E.S. Health Science Foundation, Cotignola, Italy.
| | - Lorenzo Galluzzi
- Université Paris Descartes/Paris V, Paris, France. .,Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA. .,Sandra and Edward Meyer Cancer Center, New York, NY, USA.
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Verdoia M, Kedhi E, Suryapranata H, Galasso G, Dudek D, De Luca G. Polymer-Free vs. Polymer-Coated Drug-Eluting Stents for the Treatment of Coronary Artery Disease: A Meta-Analysis of 16 Randomized Trials. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2019; 21:745-753. [PMID: 31669109 DOI: 10.1016/j.carrev.2019.10.017] [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: 07/22/2019] [Revised: 09/30/2019] [Accepted: 10/14/2019] [Indexed: 01/10/2023]
Abstract
BACKGROUND Polymer-coating represents one of components of drug-eluting stents (DES) to have experienced a more intensive technological evolution. Polymer-free DES (PF-DES) have offered promising angiographic results, with earlier complete re-endothelization, potentially reducing the thrombotic risk and offering the option of a shorter antiplatelet therapy. However, contrasting prognostic data have been reported so far with PF-DES. Therefore, the aim of the present study was to perform a comprehensive updated meta-analysis of randomized trials (RCT) comparing the impact of PF-DES vs polymer- coated DES (PC-DES) on clinical outcome. METHODS Literature and main scientific session abstracts were searched for RCTs comparing PF-DES vs PC-DES for the treatment of CAD. The primary efficacy endpoint was mortality, secondary endpoints were cardiovascular death, myocardial infarction, target lesion revascularization (TLR) and stent thrombosis. RESULTS We included 16 randomized clinical trials, with a total of 15,689 patients, including 50.6% randomized to PF-DES. At a median follow-up of 24 months, PF-DES were associated to a significant reduction in mortality as compared to PC-DES (0.82 [0.68, 0.99], p = .03, I2 = 0%; phet = 0.93). However, no significant benefit was observed in terms of cardiovascular death or major ischemic endpoints (respectively CV death: OR [95% CI] = 0.92 [0.71, 1.18] p = .50, I2 = 0.50; phet = 0.84; MI: OR [95% CI] = 1.08 [0.90, 1.29], p = .42; I2 = 0%, phet = 0.98; TLR: OR [95% CI] = 1.02 [0.78, 1.32], p = .91; I2 = 0.63 phet = 0.0003; ST: OR [95% CI] = 0.98 [0.87, 1.10], p = .72; I2 = 0% phet = 0.64). By meta-regression analysis, the mortality benefits of PF-DES were not conditioned by the rate of diabetes mellitus or acute coronary syndromes. CONCLUSIONS Based on the current meta-analysis, PF-DES are associated to a significant reduction in mortality as compared to PC-DES, but not in the occurrence of major ischemic events. Future larger studies are certainly needed to further investigate and confirm our findings, especially in particular subsets of patients, such as those with high bleeding risk or acute myocardial infarction.
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Affiliation(s)
- Monica Verdoia
- Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy
| | - Elvin Kedhi
- Department of Cardiology, ISALA Hospital, Zwolle, the Netherlands
| | | | - Gennaro Galasso
- Divisione di Cardiologia, Università degli Studi di Salerno, Italy
| | - Dariusz Dudek
- Department of Interventional Cardiology, Jagellonian University Krakow, Poland
| | - Giuseppe De Luca
- Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
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Ajmera P, Pothineni R, Chawla KK, Mantravadi SS, Jariwala PV, Vijan V, Vijan V. Real-World Use Of Ultrathin-Strut Biodegradable Polymer-Coated Sirolimus-Eluting Stents In Patients With Coronary Artery Disease: 6-Month Clinical Outcomes. Vasc Health Risk Manag 2019; 15:439-447. [PMID: 31695399 PMCID: PMC6805243 DOI: 10.2147/vhrm.s200699] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 09/16/2019] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Although a number of drug-eluting stents have been developed with different design, composition, and polymers, the search for an ideal drug-eluting stent is ongoing. The Tetriflex (Sahajanand Medical Technology, Surat, India) is a newer-generation, ultrathin (60 µm) biodegradable polymer-coated sirolimus-eluting stent (SES) designed with a unique long dual Z-link on a cobalt-chromium alloy. The present registry aimed to evaluate the safety and clinical outcomes of the Tetriflex SES at 6-month post-implantation. METHODS This was an investigator-initiated, retrospective, multicenter, single-arm, observational registry conducted at five tertiary-care centers in India. A total of 1,269 consecutive patients with coronary artery disease who underwent implantation of at least one Tetriflex SES between March 2017 and March 2018 were included. The primary outcome was considered a composite of cardiac death, myocardial infarction and target-lesion revascularization (TLR) at 6-month follow-up. Stent thrombosis was evaluated as a safety outcome at 6-month follow-up. RESULTS The mean age of patients was 54.99±10.80 years. Among 1,515 lesions treated with 1,682 Tetriflex SES, 58.3% were type C lesions. Six-month follow-up was done for 1,245 of 1,269 (98.1%) patients. At 6 months, composite events had occurred in 31 (2.5%) patients, consisting of ten (0.8%) cardiac deaths, 16 (1.3%) myocardial infarctions, and five (0.4%) TLRs. Stent thrombosis was observed in seven (0.56%) cases at 6 months. A subgroup analysis between diabetic and nondiabetic patients did not reveal any statistically significant difference for clinical outcomes at 6-month follow-up. CONCLUSION The results of the current registry outline the safety and effectiveness of the Tetriflex SES in real-world patients, as it displayed favorable clinical outcomes at 6-month follow-up, with low incidence of TLR and stent thrombosis.
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Affiliation(s)
- Prakash Ajmera
- Department of Cardiology, Malla Reddy Narayana Multispeciality Hospital, Hyderabad, Telangana 500055, India
| | - Ramesh Pothineni
- Department of Cardiology, Ramesh Hospitals, Vijayawada, Andhra Pradesh520008, India
| | - Kamal Kumar Chawla
- Department of Cardiology, Malla Reddy Narayana Multispeciality Hospital, Hyderabad, Telangana 500055, India
| | | | - Pankaj Vinod Jariwala
- Department of Cardiology, Yashoda Hospitals, Somajiguda, Hyderabad, Telangana, 500082, India
| | - Vinod Vijan
- Department of Cardiology, Vijan Cardiac and Critical Care Centre, Nashik, Maharashtra 422005, India
| | - Vikrant Vijan
- Department of Cardiology, Vijan Cardiac and Critical Care Centre, Nashik, Maharashtra 422005, India
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Yang L, Li LH, Jiang L, Pan JQ, Luo RF, Wang YB. Micelle-embedded coating with ebselen for nitric oxide generation. Med Gas Res 2019; 9:176-183. [PMID: 31898602 PMCID: PMC7802419 DOI: 10.4103/2045-9912.273955] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 06/11/2019] [Accepted: 09/08/2019] [Indexed: 02/05/2023] Open
Abstract
Nitric oxide generation is considered to be a key factor to mimic endothelial function in terms of anti-coagulation and anti-hyperplasia. Herein, ebselen which could play the similar role as glutathion peroxidase-like was loaded into micelles and was further assembled into a layer-by-layer coating. The ability of nitric oxide generation and corresponding biological effect were investigated. Endothelial-mimetic surface has now attracted huge attention in blood-contacting materials, due to its inherent ability of secreting nitric oxide. Among those categories, nitric oxide generation surface is considered to be safe and tunable in the modification of vascular biomedical devices. How to adsorb or immobilize glutathion peroxidase-like catalyst and maintain sustained/safe nitric oxide generation is full of interest. This study aimed at developing a functional coating constructed via layer-by-layer assembly to introduce the catalyst into the coating by pre-loading ebselen in micelles. We firstly introduced phenylboronic acid moiety into the micelle molecule backbone and grafted catechol moiety to chitosan backbone. Then, chitosan, micelles (containing ebselen) and heparin were adopted as polyelectrolytes and then alternatively assembled onto the substrate via layer-by-layer protocol. The catechol was conjugated to the amine groups of chitosan by Schiff base reaction to synthesize chitosan-catechol. The hydrophobic cholesterol was conjugated to the one end of the hydrophilic hyaluronic acid, and the hydroxymethylphenylboronic acid was conjugated to the other end via the esterification of carboxyl (-COOH) and hydroxyl (-OH). The modified hyaluronic acid could spontaneously form micelles in aqueous solution. Ebselen was the loaded into the as-prepared micelles. Chitosan-catechol, heparin, and micelles were alternatively assembled onto the substrate layer by layer to form a micelle-embedded coating. The micelle-embedded coating with ebselen was successfully obtained and the nitric oxide generation ability was in a safe level which was close to healthy endothelial cells. The coating could effectively inhibit platelet adhesion and smooth muscle cell proliferation. The use of ebselen preloaded into micelles could provide a sustained release of catalyst for in situ nitric oxide generation. Besides, this method could also be used to load diverse drugs and regulate desired properties. The study was approved by the Institutional Review Board of the West China Hospital in Sichuan University on March 3, 2018, with approval No. K2018044.
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Affiliation(s)
- Li Yang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan Province, China
| | - Lin-Hua Li
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan Province, China
| | - Lu Jiang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan Province, China
| | - Jun-Qiang Pan
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan Province, China
- Department of Cardiovascular Medicine, Xi’an Central Hospital, Xi’an, Shaanxi Province, China
| | - Ri-Fang Luo
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan Province, China
| | - Yun-Bing Wang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan Province, China
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Zhu YR, Jiang XX, Zhang DM. Critical regulation of atherosclerosis by the KCa3.1 channel and the retargeting of this therapeutic target in in-stent neoatherosclerosis. J Mol Med (Berl) 2019; 97:1219-1229. [DOI: 10.1007/s00109-019-01814-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 05/07/2019] [Accepted: 06/18/2019] [Indexed: 01/09/2023]
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Drug-eluting coronary stents: insights from preclinical and pathology studies. Nat Rev Cardiol 2019; 17:37-51. [PMID: 31346257 DOI: 10.1038/s41569-019-0234-x] [Citation(s) in RCA: 148] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/25/2019] [Indexed: 01/02/2023]
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Singhvi MS, Zinjarde SS, Gokhale DV. Polylactic acid: synthesis and biomedical applications. J Appl Microbiol 2019; 127:1612-1626. [PMID: 31021482 DOI: 10.1111/jam.14290] [Citation(s) in RCA: 355] [Impact Index Per Article: 59.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Revised: 03/29/2019] [Accepted: 04/16/2019] [Indexed: 12/13/2022]
Abstract
Social and economic development has driven considerable scientific and engineering efforts on the discovery, development and utilization of polymers. Polylactic acid (PLA) is one of the most promising biopolymers as it can be produced from nontoxic renewable feedstock. PLA has emerged as an important polymeric material for biomedical applications on account of its properties such as biocompatibility, biodegradability, mechanical strength and process ability. Lactic acid (LA) can be obtained by fermentation of sugars derived from renewable resources such as corn and sugarcane. PLA is thus an eco-friendly nontoxic polymer with features that permit use in the human body. Although PLA has a wide spectrum of applications, there are certain limitations such as slow degradation rate, hydrophobicity and low impact toughness associated with its use. Blending PLA with other polymers offers convenient options to improve associated properties or to generate novel PLA polymers/blends for target applications. A variety of PLA blends have been explored for various biomedical applications such as drug delivery, implants, sutures and tissue engineering. PLA and their copolymers are becoming widely used in tissue engineering for function restoration of impaired tissues due to their excellent biocompatibility and mechanical properties. The relationship between PLA material properties, manufacturing processes and development of products with desirable characteristics is described in this article. LA production, PLA synthesis and their applications in the biomedical field are also discussed.
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Affiliation(s)
- M S Singhvi
- Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune, India
| | - S S Zinjarde
- Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune, India
| | - D V Gokhale
- CSIR-National Chemical Laboratory, NCIM Resource Centre, Pune, India
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Chen YL, Fan J, Chen G, Cao L, Lu L, Xu Y, Yin Y. Polymer-free drug-eluting stents versus permanent polymer drug-eluting stents: An updated meta-analysis. Medicine (Baltimore) 2019; 98:e15217. [PMID: 30985722 PMCID: PMC6485796 DOI: 10.1097/md.0000000000015217] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Polymer-free drug-eluting stents (PF-DES) have been demonstrated comparable to permanent polymer drug-eluting stents (PP-DES) during long-term follow-up. As a critical component of drug-eluting stents, antiproliferative drugs may be a confounding factor for the results. Thus, we sought to compare the outcomes of these stents during long-term follow-up, especially in consideration of different stent platforms with the same drugs. METHODS A systemic search was performed to identify the related randomized controlled trials comparing PF-DES with PP-DES. Primary outcomes included short (≤1 year) and long-term (>1 year) target lesion revascularization (TLR), short-term in-stent late luminal loss (LLL) and diameter stenosis (DS). Subgroup analyses stratified by the different platforms with the same proliferative drugs were conducted in TLR, LLL, and DS. Standardized mean differences (SMDs) and risk ratios (RRs) were estimated using fixed /random effects models RESULTS:: A total of 6927 patients extracted from 12 RCTs were enrolled in the meta-analysis. No differences were observed in clinical outcomes of short-term and long-term overall mortality, myocardial infarction and stent thrombosis and angiographic outcomes of short-term in-stent LLL and DS between PF-DES and PP-DES for patients with coronary artery lesions. Nevertheless, compared with PP-DES coated with the same proliferative drugs, PF-DES had significantly increased risks of in-stent LLL (SMD, 0.49; 95% confidence interval [CI], 0.25-0.72) and DS (SMD, 0.67; 95% CI, 0.27-1.07), and long-term TLR (RR, 1.64; 95% CI 1.13-2.39). There were no significant differences in other outcomes. CONCLUSIONS Under the condition of using same antiproliferative drugs (paclitaxel or sirolimus) in different stent systems, PF-DES are associated with the increased risk of restenosis compared to PP-DES.
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Talha M, Ma Y, Kumar P, Lin Y, Singh A. Role of protein adsorption in the bio corrosion of metallic implants - A review. Colloids Surf B Biointerfaces 2019; 176:494-506. [PMID: 30690385 DOI: 10.1016/j.colsurfb.2019.01.038] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 12/14/2018] [Accepted: 01/19/2019] [Indexed: 11/15/2022]
Abstract
Implants are exposed to a complex physiological environment that contains various organic compounds, especially proteins. The adsorption of proteins has an immense influence on the corrosion, biocompatibility and wear properties of implantable metals. Proteins engage in multiple processes that could potentially inhibit or promote metal degradation, depending on the type of proteins, their concentration and the properties of the implant material. In the bio corrosion process, proteins are denatured and transform into a film on the metal surface, inhibiting corrosion. This film is found on many retrieved artificial joints, especially on worn areas, and can protect the passive film from scrapping due to its lubricating effect, thus decreasing tribocorroion. On the other hand, the interactions of metal ions with proteins (and amino acids) create colloidal organometallic complexes. Transport of the complex compounds away from the interface increases dissolution rates; thus, it accelerates the corrosion of metallic implants. The influence of protein adsorption on the corrosion behaviour of metallic biomaterials is presented in this review. Biocompatible metals that are favourably used as implants such as stainless steel, Co-Cr alloys, Ti alloys and biodegradable Mg and Fe alloys are specifically addressed. We have highlighted the adsorption phenomenon of protein on metallic implants, the interaction of proteins with metallic implants and the role of protein adsorption on implant biocorrosion behaviour as well as their wear resistance.
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Affiliation(s)
- Mohd Talha
- State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation, Southwest Petroleum University, Chengdu, 610500, Sichuan, China; School of Materials Science and Engineering, Southwest Petroleum University, Chengdu, 610500, Sichuan, China
| | - Yucong Ma
- School of Materials Science and Engineering, Southwest Petroleum University, Chengdu, 610500, Sichuan, China
| | - Pardeep Kumar
- Department of Physics, Guru Jambheshwar University of Science and Technology, Hisar, 125001, Haryana, India
| | - Yuanhua Lin
- State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation, Southwest Petroleum University, Chengdu, 610500, Sichuan, China; School of Materials Science and Engineering, Southwest Petroleum University, Chengdu, 610500, Sichuan, China.
| | - Ambrish Singh
- State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation, Southwest Petroleum University, Chengdu, 610500, Sichuan, China; School of Materials Science and Engineering, Southwest Petroleum University, Chengdu, 610500, Sichuan, China
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Poly-ε-caprolactone/polysulfhydrylated polyester blend: A platform for topical and degradable nitric oxide-releasing materials. Eur Polym J 2018. [DOI: 10.1016/j.eurpolymj.2018.09.046] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
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40 Years of Percutaneous Coronary Intervention: History and Future Directions. J Pers Med 2018; 8:jpm8040033. [PMID: 30275411 PMCID: PMC6313463 DOI: 10.3390/jpm8040033] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 09/26/2018] [Accepted: 09/26/2018] [Indexed: 01/06/2023] Open
Abstract
The field of interventional cardiology has evolved significantly since the first percutaneous transluminal coronary angioplasty was performed 40 years ago. This evolution began with a balloon catheter mounted on a fixed wire and has progressed into bare-metal stents (BMS), first-generation drug-eluting stents (DES), second- and third-generation biodegradable polymer-based DES, and culminates with the advent of bioabsorbable stents, which are currently under development. Each step in technological advancement has improved outcomes, while new persisting challenges arise, caused by the stent scaffolds, the polymers employed, and the non-selective cytostatic and cytotoxic drugs eluted from the stents. Despite the promising technological advances made in stent technology, managing the balance between reductions in target lesion revascularization, stent thrombosis, and bleeding remain highly complex issues. This review summarizes the evolution of percutaneous coronary intervention with a focus on vascular dysfunction triggered by the non-selective drugs eluted from various stents. It also provides an overview of the mechanism of action of the drugs currently used in DES. We also discuss the efforts made in developing novel cell-selective drugs capable of inhibiting vascular smooth muscle cell (VSMC) proliferation, migration, and infiltration of inflammatory cells while allowing for complete reendothelialization. Lastly, in the era of precision medicine, considerations of patients’ genetic variance associated with myocardial infarction and in-stent restenosis are discussed. The combination of personalized medicine and improved stent platform with cell-selective drugs has the potential to solve the remaining challenges and improve the care of coronary artery disease patients.
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Tang XF, Ma YL, Song Y, Xu JJ, Yao Y, He C, Wang HH, Jiang P, Jiang L, Liu R, Gao Z, Zhao XY, Qiao SB, Yang YJ, Gao RL, Xu B, Yuan JQ. Biodegradable polymer drug-eluting stents versus second-generation drug-eluting stents in patients with and without diabetes mellitus: a single-center study. Cardiovasc Diabetol 2018; 17:114. [PMID: 30107794 PMCID: PMC6090623 DOI: 10.1186/s12933-018-0758-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Accepted: 08/11/2018] [Indexed: 01/14/2023] Open
Abstract
Background To improve outcomes in patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention remain an unmet clinical need. The study aimed to evaluate the efficacy and safety of G2-DESs and BP-DESs in patients with and without DM in a single center in China. Methods A total of 7666 consecutive patients who exclusively had G2-DES or BP-DES implantation throughout 2013 in our center were studied. The primary efficacy endpoint was any target lesion revascularization (TLR), whereas the primary safety endpoint was a composite of death or myocardial infarction (MI) at 2-year follow-up. Results G2-DESs had a similar occurrence of death, non-fatal MI, TLR, stroke, and stent thrombosis compared with BP-DESs in patients with DM (all P > 0.05). The incidence of TVR and TLR was lower for G2-DESs than for BP-DESs in patients without DM (3.2% vs. 5.1%, P = 0.002; 2.2% vs. 4.5%, P < 0.001, respectively). Kaplan–Meier analysis also showed better TVR- and TLR-free survival rates for G2-DESs than for BP-DESs in patients without DM. Multivariate analysis showed that a BP-DES was an independent risk factor for TLR (hazard ratio 1.963, 95% confidence interval 1.390–2.772, P < 0.001) in patients without DM, which was not predictive of other components of major adverse cardiac events (P > 0.05). Conclusions G2-DESs have better efficacy, represented by a reduced risk of TLR, and similar safety compared with BP-DESs in patients without DM. G2-DESs have similar efficacy and safety compared with BP-DESs in patients with DM at 2-year follow-up. Electronic supplementary material The online version of this article (10.1186/s12933-018-0758-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Xiao-Fang Tang
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Yuan-Liang Ma
- Department of Cardiology, Xuanwu Hospital Capital Medical University, No. 45 Changchun Road, Xicheng District, Beijing, China
| | - Ying Song
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Jing-Jing Xu
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Yi Yao
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Chen He
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Huan-Huan Wang
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Ping Jiang
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Lin Jiang
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Ru Liu
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Zhan Gao
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Xue-Yan Zhao
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Shu-Bin Qiao
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Yue-Jin Yang
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Run-Lin Gao
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Bo Xu
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China
| | - Jin-Qing Yuan
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road 167, Xicheng District, Beijing, Postal code: 100037, China.
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Ma YL, Tang XF, Yao Y, Xu N, Song Y, Jiang P, Xu JJ, Wang HH, Jiang L, Liu R, Zhao XY, Chen J, Gao Z, Qiao SB, Yang YJ, Gao RL, Xu B, Yuan JQ. Comparison of Efficacy and Safety between First- and Second-Generation Drug-Eluting Stents in Patients with Acute Coronary Syndrome. Chin Med J (Engl) 2018; 131:1397-1405. [PMID: 29893356 PMCID: PMC6006822 DOI: 10.4103/0366-6999.233959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background: It remains undetermined whether second-generation drug-eluting stents (G2-DESs) outperform first-generation DESs (G1-DESs) in patients with acute coronary syndrome (ACS). We aimed to compare the efficacy and safety of G1-DES and G2-DES in ACS patients in a high-volume cardiovascular center. Methods: In 2013, 10,724 consecutive patients underwent percutaneous coronary intervention in our institution. We included 4037 patients with ACS who underwent exclusively G1-DES or G2-DES implantation (n = 364 and n = 3673, respectively). We used propensity score matching to minimize the imbalance between the G1-DES and G2-DES groups and followed patients for 2 years. The efficacy endpoints were major adverse cardiac events (MACEs) and its components including target vessel-related myocardial infarction (TV-MI), target vessel revascularization/target lesion revascularization (TVR/TLR), and cardiac death. The safety endpoint was stent thrombosis. Continuous variables were compared by Mann-Whitney U-test, and categorical variables were compared using Pearson's Chi-square or Fisher's exact test. Kaplan-Meier curves were constructed to compare the event-free survival rates, and multivariate Cox proportional hazards regression analysis was used to assess whether stent type was an independent risk factor for the efficacy and safety endpoints. Results: At the 2-year follow-up, the results for MACE and it components, as well as stent thrombosis, were similar for G1-DES and G2-DES (MACE, 5.2% vs. 4.3%, χ2 = 0.514, P = 0.474; TV-MI, 0.8% vs. 0.4%, P = 0.407; TVR, 4.9% vs. 3.7%, χ2 = 0.939, P = 0.333; TLR, 3.8% vs. 2.5%, χ2 = 1.610, P = 0.205; cardiac death, 0.3% vs. 0.5%, P = 0.670; and stent thrombosis, 0.5% vs. 0.4%, P > 0.999). Kaplan-Meier analysis indicated similar event-free survival rates between G1-DES and G2-DES after propensity score matching (all: log-rank P > 0.05). Multivariate analysis demonstrated that stent type was not an independent risk factor for the efficacy and safety endpoints (MACE, hazard ratio [HR] = 0.805, 95% confidence interval [CI]: 0.455–1.424, P = 0.456; TV-MI, HR = 0.500, 95% CI: 0.101–2.475, P = 0.395; TVR, HR = 0.732, 95% CI: 0.403–1.330, P = 0.306; TLR, HR = 0.629, 95% CI: 0.313–1.264, P = 0.193; cardiac death, HR = 1.991, 95% CI: 0.223–17.814, P = 0.538; and stent thrombosis, HR = 0.746, 95% CI: 0.125–4.467, P = 0.749). Conclusion: G1-DES and G2-DES have similar efficacy and safety profiles in ACS patients at the 2-year follow-up.
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Affiliation(s)
- Yuan-Liang Ma
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Xiao-Fang Tang
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Yi Yao
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Na Xu
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Ying Song
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Ping Jiang
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Jing-Jing Xu
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Huan-Huan Wang
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Lin Jiang
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Ru Liu
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Xue-Yan Zhao
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Jue Chen
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Zhan Gao
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Shu-Bin Qiao
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Yue-Jin Yang
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Run-Lin Gao
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Bo Xu
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Jin-Qing Yuan
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
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Nogic J, Baey YW, Nerlekar N, Ha FJ, Cameron JD, Nasis A, West NE, Brown AJ. Polymer-free versus permanent polymer-coated drug eluting stents for the treatment of coronary artery disease: A meta-analysis of randomized trials. J Interv Cardiol 2018; 31:608-616. [DOI: 10.1111/joic.12522] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 04/22/2018] [Accepted: 05/01/2018] [Indexed: 11/30/2022] Open
Affiliation(s)
- Jason Nogic
- Monash Cardiovascular Research Centre; Monash University and Monash Heart, Monash Health; Melbourne Victoria Australia
| | - Yi-Wei Baey
- Monash Cardiovascular Research Centre; Monash University and Monash Heart, Monash Health; Melbourne Victoria Australia
| | - Nitesh Nerlekar
- Monash Cardiovascular Research Centre; Monash University and Monash Heart, Monash Health; Melbourne Victoria Australia
| | - Francis J. Ha
- Monash Cardiovascular Research Centre; Monash University and Monash Heart, Monash Health; Melbourne Victoria Australia
| | - James D. Cameron
- Monash Cardiovascular Research Centre; Monash University and Monash Heart, Monash Health; Melbourne Victoria Australia
| | - Arthur Nasis
- Monash Cardiovascular Research Centre; Monash University and Monash Heart, Monash Health; Melbourne Victoria Australia
| | - Nick E.J. West
- Department of Interventional Cardiology; Papworth Hospital NHS Trust; Cambridge UK
| | - Adam J. Brown
- Monash Cardiovascular Research Centre; Monash University and Monash Heart, Monash Health; Melbourne Victoria Australia
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Tzafriri AR, Garcia-Polite F, Li X, Keating J, Balaguer JM, Zani B, Bailey L, Markham P, Kiorpes TC, Carlyle W, Edelman ER. Defining drug and target protein distributions after stent-based drug release: Durable versus deployable coatings. J Control Release 2018; 274:102-108. [PMID: 29421608 DOI: 10.1016/j.jconrel.2018.02.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Revised: 12/31/2017] [Accepted: 02/04/2018] [Indexed: 11/19/2022]
Abstract
BACKGROUND Innovations in drug eluting stent designs make it increasingly important to develop models for differentiating performance through spatial definition of drug, receptor binding and cell state. METHODS Two designs of sirolimus analog eluting stents were implanted into porcine coronary arteries for 28, 60 or 90 days (n = 9/time point), durable coating (Xience) and deployable absorbable coating (MiStent). Explanted arteries were evaluated for drug content (n = 3/time point) by LC-MS/MS and for drug and target protein (mTOR) distributions by immunofluorescence (IF, n = 6/time point). A computational model was developed to predict drug release and arterial distribution maps. RESULTS Both stents released the majority of drug load by 28 days, with different tissue retention efficiencies (91.4 ± 4.9% MiStent versus 21.5 ± 1.9% Xience, P < 0.001). Computational modeling of MiStent coating deployment and microcrystal dissolution recapitulated in vivo drug release and net tissue content and predicted that >98.5% of deployed drug remains crystalline through 90 days. Immunofluorescence and computational modeling showed peristrut drug localization for both stents, with similar peaks, but high interstrut levels only at sites of coating deployment from the absorbable coating. Co-localization of mTOR-IF with drug-IF for both devices showed persistent drug effects, though with differential drug-receptor pharmacokinetics. CONCLUSIONS Immunofluorescence and computational modeling provide insights into drug distribution and binding status that can help differentiate drug delivery technologies. Herein we found that tissue deployment of slow dissolving crystalline drug particles results in temporally and spatially more uniform drug delivery to interstrut zones that might otherwise be under-dosed without excess peristrut drug.
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Affiliation(s)
| | | | - Xiaojian Li
- CBSET Inc., 500 Shire Way, Lexington, MA, USA
| | | | | | - Brett Zani
- CBSET Inc., 500 Shire Way, Lexington, MA, USA
| | - Lynn Bailey
- CBSET Inc., 500 Shire Way, Lexington, MA, USA
| | | | | | | | - Elazer R Edelman
- IMES, MIT, 77 Massachusetts Avenue, Cambridge, MA, USA; Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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Zhou Y, Chen S, Huang L, Hildick-Smith D, Ferenc M, Jabbour RJ, Azzalini L, Colombo A, Chieffo A, Zhao X. Definite stent thrombosis after drug-eluting stent implantation in coronary bifurcation lesions: A meta-analysis of 3,107 patients from 14 randomized trials. Catheter Cardiovasc Interv 2017; 92:680-691. [PMID: 29214736 DOI: 10.1002/ccd.27443] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2017] [Revised: 10/06/2017] [Accepted: 11/11/2017] [Indexed: 01/17/2023]
Affiliation(s)
- Yu Zhou
- Institution of Cardiovascular Research, Xinqiao Hospital, Third Military Medical University; Chongqing China
| | - Shengda Chen
- State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University; China
- IBiTech, bioMMeda, Department of Electronics and Information Systems, iMinds Medical IT Department; Ghent University; De Pintelaan Ghent Belgium
| | - Lan Huang
- Institution of Cardiovascular Research, Xinqiao Hospital, Third Military Medical University; Chongqing China
| | - David Hildick-Smith
- Sussex Cardiac Centre; Brighton and Sussex University Hospitals; Brighton United Kingdom
| | - Miroslaw Ferenc
- The Division of Cardiology and Angiology II; University Heart Center Freiburg - Bad Krozingen, Suedring 15, Bad Krozingen; Germany
| | | | | | | | - Alaide Chieffo
- Cardiology Department; San Raffaele Hospital; Milan Italy
| | - Xiaohui Zhao
- Institution of Cardiovascular Research, Xinqiao Hospital, Third Military Medical University; Chongqing China
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Alexander GC, Hwang PTJ, Chen J, Kim J, Brott BC, Yoon YS, Jun HW. Nanomatrix Coated Stent Enhances Endothelialization but Reduces Platelet, Smooth Muscle Cell, and Monocyte Adhesion under Physiologic Conditions. ACS Biomater Sci Eng 2017; 4:107-115. [PMID: 31538110 DOI: 10.1021/acsbiomaterials.7b00676] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cardiovascular disease is presently the number one cause of death worldwide. Current stents used to treat cardiovascular disease have a litany of unacceptable shortcomings: adverse clinical events including restenosis, neointimal hyperplasia, thrombosis, inflammation, and poor re-endothelialization. We have developed a biocompatible, multifunctional, peptide amphiphile-based nanomatrix coating for stents. In this study, we evaluated the ability of the nanomatrix coated stent to simultaneously address the issues facing current stents under physiological flow conditions in vitro. We found that the nanomatrix coated stent could increase endothelial cell migration, adhesion, and proliferation (potential for re-endothelialization), discourage smooth muscle cell migration and adhesion (potential to reduce neointimal hyperplasia and restenosis), and decrease both platelet activation and adhesion (potential to prevent thrombosis) as well as monocyte adhesion (potential to attenuate inflammatory responses) under physiological flow conditions in vitro. These promising results demonstrate the potential clinical utility of this nanomatrix stent coating, and highlight the importance of biocompatibility, multifunctionality, and bioactivity in cardiovascular device design.
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Affiliation(s)
- G C Alexander
- Department of Biomedical Engineering, University of Alabama at Birmingham, 806 Shelby Building, 1825 University Boulevard, Birmingham, Alabama 35294, United States
| | - P T J Hwang
- Department of Biomedical Engineering, University of Alabama at Birmingham, 806 Shelby Building, 1825 University Boulevard, Birmingham, Alabama 35294, United States
| | - J Chen
- Department of Biomedical Engineering, University of Alabama at Birmingham, 806 Shelby Building, 1825 University Boulevard, Birmingham, Alabama 35294, United States
| | - J Kim
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, 806 Shelby Building, 1825 University Boulevard, Birmingham, Alabama 35294, United States
| | - B C Brott
- School of Medicine, Division of Cardiology, University of Alabama at Birmingham, 806 Shelby Building, 1825 University Boulevard, Birmingham, Alabama 35294, United States
| | - Y S Yoon
- School of Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, United States.,Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea
| | - H-W Jun
- Department of Biomedical Engineering, University of Alabama at Birmingham, 806 Shelby Building, 1825 University Boulevard, Birmingham, Alabama 35294, United States
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