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IHD encompasses a spectrum of conditions, including atherosclerosis (AS), myocardial infarction (MI), and ischemia\/reperfusion (I\/R) injury. Programmed cell death (PCD) of endothelial cells (ECs) plays a critical role in IHD pathogenesis, causing microvascular dysfunction, barrier disruption and exacerbation of cardiac injury. PCD involves different signaling pathways, but they are interconnected. Therefore, it is crucial to understand the mechanisms underlying the various forms of PCD in ECs to develop therapeutic strategies for IHD. This review focuses on the molecular mechanisms of PCD of ECs in IHD and provides comprehensive summary of potential cell and gene therapy therapeutic strategies for the treatment of IHD.<\/jats:p>","DOI":"10.3390\/bioengineering13060661","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T01:23:21Z","timestamp":1780622601000},"page":"661","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Programmed Cell Death of Endothelial Cells in Ischemic Heart Disease: Mechanism and Potential Cell and Gene Therapeutic Prospects"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7405-379X","authenticated-orcid":false,"given":"Zijia","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Rehabilitation, Children\u2019s Hospital of Nanjing Medical University, Nanjing 210003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China"},{"name":"National Heart Centre Singapore, Singapore 169609, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Cao","sequence":"additional","affiliation":[{"name":"Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6193-8516","authenticated-orcid":false,"given":"Bingyang","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China"},{"name":"Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2794-7387","authenticated-orcid":false,"given":"Lintao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Children\u2019s Hospital of Nanjing Medical University, Nanjing 210003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global Burden of Cardiovascular Diseases and Risk Factors, 1990\u20132019: Update from the GBD 2019 Study","volume":"76","author":"Roth","year":"2020","journal-title":"J. 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