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It has been shown that poly(I:C) exhibited cardioprotective activities through the PI3K\/Akt pathway, which is the main signal transduction pathway during autophagy. However, the precise mechanism by whether poly(I:C) regulates autophagy remains poorly understood. Thus, this study was designed to investigate the therapeutic effect of poly(I:C) against MIRI and the underlying pathway connection with autophagy. We demonstrated that 1.25 and 5\u00a0mg\/kg poly(I:C) preconditioning significantly reduced myocardial infarct size and cardiac dysfunction. Moreover, poly(I:C) significantly promoted cell survival by restoring autophagy flux and then regulating it to an adequate level Increased autophagy protein Beclin1 and LC3II together with p62\u00a0degradation after additional chloroquine. In addition, mRFP\u2010GFP\u2010LC3 adenoviruses exhibited autophagy activity in neonatal rat cardiac myocytes (NRCMs). Mechanistically, poly(I:C) activated the PI3K\/AKT\/mTOR pathway to induce autophagy, which was abolished by LY294002 (PI3K antagonist), rapamycin (autophagy activator and mTOR inhibitor), or 3\u2010methyladenine (autophagy inhibitor), suggesting either inhibition of the PI3K\/Akt\/mTOR pathway or autophagy activity interrupt the beneficial effect of poly(I:C) preconditioning. In conclusion, poly(I:C) promotes cardiomyocyte survival from ischemia\/reperfusion injury by regulating autophagy via the PI3K\/Akt\/mTOR pathway.<\/jats:p>","DOI":"10.1096\/fj.202101220rr","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T14:27:40Z","timestamp":1650378460000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Poly(I:C) attenuates myocardial ischemia\/reperfusion injury by restoring autophagic function"],"prefix":"10.1096","volume":"36","author":[{"given":"Erya","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Anesthesiology West China Hospital Sichuan University  Chengdu China"},{"name":"Laboratory of Anesthesia and Critical Care Medicine, National Clinical Research Center for Geriatrics Translational Neuroscience Center The\u00a0Research Units of West China Chinese Academy of Medical Science  Chengdu 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