{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:51:58Z","timestamp":1792270318953,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T00:00:00Z","timestamp":1562112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570277"],"award-info":[{"award-number":["81570277"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The surged systemic vascular inflammation after acute myocardial infarction (AMI) aggravates the atherosclerotic endothelial injury. To explore roles of miR\u2010499 released from cardiomyocytes during AMI in endothelial injury. Using qPCR and ELISA, we discovered that patients with AMI had significantly increased plasma miR\u2010499, which was directly correlated with serum thrombomodulin, a marker for endothelial injury. Plasma of AMI patients, when incubated with human umbilical vein endothelial cells (HUVECs), significantly increased the expression of endothelial injury markers, which could be abrogated by antagomiR\u2010499. In vitro, neonatal rat cardiomyocytes subjected to hypoxia\/reoxygenation (HX\/R) released miR\u2010499 that could be internalized into rat pulmonary microvascular endothelial cells (RPMECs), worsening the high glucose\u2010induced injury. In silico analysis demonstrated that CHRNA7 encoding \u03b17\u2010nAchR is a target of miR\u2010499, which was validated in cell lines expressing endogenous \u03b17\u2010nAchR. In high glucose\u2010induced RPMECs injury model, miR\u2010499 aggravated, whereas forced CHRNA7 expression ameliorated the injury. Moreover, the perfusate from Langendorff perfused rat heart subjected to HX\/R contained higher level of miR\u2010499 that significantly impaired the Bradykinin\u2010mediated endothelium\u2010dependent relaxation in both conduit and resistance arteries, which could be partially abrogated by antagomiR\u2010499. Finally, the correlation between plasma miR\u2010499 and endothelial injury was further confirmed in another cohort of AMI patients. We conclude that miR\u2010499 released from injured cardiomyocytes contributes to the endothelial injury by targeting \u03b17\u2010nAchR. This study implies that miR\u2010499 may serve as a potential target for the treatment of the surged vascular inflammation post\u2010AMI.<\/jats:p>","DOI":"10.1111\/jcmm.14474","type":"journal-article","created":{"date-parts":[[2019,7,4]],"date-time":"2019-07-04T03:21:00Z","timestamp":1562210460000},"page":"6085-6097","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["miR\u2010499 released during myocardial infarction causes endothelial injury by targeting \u03b17\u2010nAchR"],"prefix":"10.1111","volume":"23","author":[{"given":"Rui","family":"Zhou","sequence":"first","affiliation":[{"name":"The Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Institute of Cardiovascular Research Southwest Medical University Stockholm 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