{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:27:59Z","timestamp":1787783279100,"version":"build-2784847793"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to identify circulating exosomal microRNAs for early detection of coronary microvascular dysfunction (MD) and stratification of myocardial injury risk in type 2 diabetes, and to test whether miR-550a-5p derived from endothelial cell models mechanistically links endothelial stress to cardiomyocyte vulnerability via Hippo\u2013eNOS signaling and vesicular transfer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      We combined Gene Expression Omnibus (GEO)-guided discovery and compendium prioritization with clinical and mechanistic validation. Plasma exosomal miR-550a-5p\/miR-665 were quantified in a well-phenotyped Type 2 Diabetes Mellitus (T2DM) cohort and related to MD and myocardial injury.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , miR-550a-5p was modulated in human cardiac microvascular endothelial cells under high glucose to profile Hippo\u2013YAP\/eNOS signaling, and its exosomal transfer effects on human cardiomyocytes were evaluated, with Hippo inhibition applied as a rescue strategy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>Exosomal miR-550a-5p and miR-665 were elevated in MD and further increased with myocardial injury, showing useful diagnostic performance and independent associations. miR-550a-5p inhibition restored endothelial viability, migration, tube formation and p-eNOS\/eNOS, reduced MST1\/LATS1 activation, and increased Yes-associated protein (YAP) activity. Endothelial exosomes delivered miR-550a-5p to cardiomyocytes, aggravating apoptosis and oxidative stress; donor-cell miR-550a-5p suppression and Hippo inhibition mitigated these effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Exosomal miR-550a-5p, together with miR-665, functions as a dual-utility signal, serving as an accessible biomarker for coronary MD and as a mechanistic mediator in endothelial-to-cardiomyocyte exosomal signaling. These findings support earlier detection, risk stratification, and mechanism-guided intervention in T2DM. Future priorities include external validation, longitudinal kinetic assessment, and target-network mapping.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1744708","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T06:42:27Z","timestamp":1769668947000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Circulating exosomal miR-550a-5p\/miR-665 identify coronary microvascular dysfunction and drive endothelial\u2013myocyte crosstalk in type 2 diabetes"],"prefix":"10.3389","volume":"14","author":[{"given":"Xiudong","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The 8th Medical Center of PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangliang","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The 8th Medical Center of PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The 8th Medical Center of PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueming","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The 8th Medical Center of PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghui","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The 8th Medical Center of PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, No 984 Hospital of PLA","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghong","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion, The 8th Medical Center of PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The 8th Medical Center of PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/s41569-019-0200-7","article-title":"Molecular mechanisms of arrhythmogenic cardiomyopathy","volume":"16","author":"Austin","year":"2019","journal-title":"Nat. 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