{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T20:26:06Z","timestamp":1789244766418,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Viral myocarditis (VMC) is a common myocardial inflammatory disease characterized by inflammatory cell infiltration and cardiomyocyte necrosis. Sema3A was reported to reduce cardiac inflammation and improve cardiac function after myocardial infarction, but its role in VMC remains to be explored. Here, a VMC mouse model was established by infection with CVB3, and Sema3A was overexpressed in vivo by intraventricular injection of an adenovirus\u2010mediated Sema3A expression vector (Ad\u2010Sema3A). We found that Sema3A overexpression attenuated CVB3\u2010induced cardiac dysfunction and tissue inflammation. And Sema3A also reduced macrophage accumulation and NLRP3 inflammasome activation in the myocardium of VMC mice. In vitro, LPS was used to stimulate primary splenic macrophages to mimic the macrophage activation state in vivo. Activated macrophages were co\u2010cultured with primary mouse cardiomyocytes to evaluate macrophage infiltration\u2010induced cardiomyocyte damage. Ectopic expression of Sema3A in cardiomyocytes effectively protected cardiomyocytes from activated macrophage\u2010induced inflammation, apoptosis, and ROS accumulation. Mechanistically, cardiomyocyte\u2010expressed Sema3A mitigated macrophage infiltration\u2010caused cardiomyocyte dysfunction by promoting cardiomyocyte mitophagy and hindering NLRP3 inflammasome activation. Furthermore, NAM (a SIRT1 inhibitor) reversed the protective effect of Sema3A against activated macrophage\u2010induced cardiomyocyte dysfunction by suppressing cardiomyocyte mitophagy. In conclusion, Sema3A promoted cardiomyocyte mitophagy and suppressed inflammasome activation by regulating SIRT1, thereby attenuating macrophage infiltration\u2010induced cardiomyocyte injury in VMC.<\/jats:p>","DOI":"10.1002\/tox.23765","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T05:12:14Z","timestamp":1678165934000},"page":"1305-1317","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>Sema3A<\/scp>\n                    alleviates viral myocarditis by modulating\n                    <scp>SIRT1<\/scp>\n                    to regulate cardiomyocyte mitophagy"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0134-234X","authenticated-orcid":false,"given":"Lin","family":"Lin","sequence":"first","affiliation":[{"name":"Cardiovascular Hospital of the Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an 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