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This study elucidated the role of Estrogen\u2010Related Receptor Gamma (ERR\u03b3) in modulating the inflammatory response post\u2010MI, demonstrating that ERR\u03b3 expression was downregulated in ischemic tissue and hypoxic neonatal mouse ventricular myocytes (NMVMs). Cardiomyocyte\u2010specific overexpression of ERR\u03b3 reduced infarct size, improved cardiac function, and suppressed excessive myocardial inflammation and pyroptosis by binding to the GBP5 promoter, thereby inhibiting GBP5 transcription and reducing NLRP3 inflammasome assembly. The protective effects of ERR\u03b3 overexpression were reversed by overexpressing GBP5, and the ERR\u03b3 agonist DY131 also improved cardiac function after MI. These findings suggest that ERR\u03b3 activation reduces myocardial ischemic injury by regulating cardiomyocyte inflammation and pyroptosis, highlighting ERR\u03b3 as a potential novel therapeutic target for attenuating post\u2010MI injury.<\/jats:p>","DOI":"10.1096\/fj.202500763r","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:15:45Z","timestamp":1752138945000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Nuclear Receptor\n                    <scp>ERR\u03b3<\/scp>\n                    Protects Against Cardiac Ischemic Injury by Suppressing\n                    <scp>GBP5<\/scp>\n                    \u2010Mediated Myocardial Inflammation"],"prefix":"10.1096","volume":"39","author":[{"given":"Junhao","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Cardiology, Xinhua Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai 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