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However, ischemia\u2013reperfusion exacerbates cardiac damage. Vascular endothelial cell\u2013derived small extracellular vesicles play a pivotal role in ischemia\u2013reperfusion injury; although the underlying mechanisms remain poorly understood. Therefore, this study aimed to elucidate the mechanisms of vascular endothelial cell\u2013derived small extracellular vesicles and investigate their potential therapeutic roles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Small extracellular vesicles derived from vascular endothelial cells were isolated using ultracentrifugation, and their characteristics were confirmed using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Their effects on myocardial injury was evaluated in vivo using a mouse myocardial ischemia\u2013reperfusion model, and their role was further examined in vitro using a cellular hypoxia\/reoxygenation model. The key micro ribonucleic acid in small extracellular vesicles was screened via high-throughput sequencing, and its regulatory effect on cardiomyocyte apoptosis was verified in vitro through intervention experiments. The key gene was predicted using miRanda and TargetScan, and the related interaction was verified by a dual-luciferase reporter assay and ribonucleic acid immunoprecipitation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our in vivo study revealed that small extracellular vesicles significantly attenuated ischemia\u2013reperfusion-induced cardiomyocyte apoptosis and improved cardiac function. We also analyzed micro ribonucleic acid expression in small extracellular vesicles and found that miR410-3p was highly expressed and associated with cellular apoptosis. In vitro experiments demonstrated that small extracellular vesicles increased miR410-3p expression in cardiomyocytes and that miR410-3p effectively inhibited cardiomyocyte apoptosis in a cellular ischemia\u2013reperfusion model. Conversely, miR410-3p inhibition attenuated the protective effect of small extracellular vesicles. Moreover, we found that SMAD family member 7 is one of the target messenger ribonucleic acids of miR410-3p and affects cellular apoptosis by modulating nuclear factor kappa-light-chain-enhancer of activated B cells. Cellular experiments verified that the antiapoptotic effect of miR410-3p was neutralized by SMAD family member 7 overexpression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results revealed that vascular endothelial cell\u2013derived small extracellular vesicles attenuate ischemia\u2013reperfusion-induced cardiomyocyte apoptosis via the miR410-3p\/SMAD family member 7 axis. This study provides valuable insights into the molecular mechanisms underlying ischemia\u2013reperfusion-induced myocardial damage and highlights potential therapeutic opportunities for mitigating it.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03000605261435745","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T03:35:13Z","timestamp":1776310513000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Vascular endothelial cell\u2013derived small extracellular vesicles: A protective role against cardiomyocyte apoptosis in ischemia\u2013reperfusion injury through miR410-3p-modulated\n                    <i>smad7<\/i>\n                    pathway"],"prefix":"10.1177","volume":"54","author":[{"given":"Xiaoqiang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of 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