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Here, we test the hypothesis that short\u2010term non\u2010ischaemic stimulation of hypertrophy renders the heart resistant to subsequent ischaemic injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>Transient transverse aortic constriction (TAC) was performed for 3\u00a0days in mice and then withdrawn for 4\u00a0days by aortic debanding, followed by subsequent exposure to myocardial ischaemia\u2010reperfusion (I\/R) injury. Following I\/R injury, myocardial infarct size and apoptosis were significantly decreased, and cardiac dysfunction was markedly improved in the TAC preconditioning group compared with the control group. Mechanistically, TAC preconditioning markedly suppressed I\/R\u2010induced autophagy and preserved autophagic flux by deacetylating SOD2 via a SIRT3\u2010dependent mechanism. Moreover, treatment with an adenovirus encoding SIRT3 partially mimicked the effects of hypertrophic preconditioning, whereas genetic ablation of SIRT3 in mice blocked the cardioprotective effects of hypertrophic preconditioning. Furthermore, in vivo lentiviral\u2010mediated knockdown of Beclin 1 in the myocardium ameliorated the I\/R\u2010induced impairment of autophagic flux and was associated with a reduction in cell death, whereas treatment with a lentivirus encoding Beclin 1 abolished the cardioprotective effect of TAC preconditioning.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study identifies TAC preconditioning as a novel strategy for induction of an endogenous self\u2010defensive and cardioprotective mechanism against cardiac injury. Specifically, TAC preconditioning reduced myocardial autophagic cell death in a SIRT3\/SOD2 pathway\u2010dependent manner.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.13051","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T17:09:03Z","timestamp":1620752943000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Hypertrophic Preconditioning Attenuates Myocardial Ischaemia\u2010Reperfusion Injury by Modulating SIRT3\u2010SOD2\u2010mROS\u2010Dependent Autophagy"],"prefix":"10.1111","volume":"54","author":[{"given":"Lei\u2010Lei","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Cardiology Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University  Shanghai China"},{"name":"NHC Key Laboratory of Viral Heart Diseases  Shanghai China"},{"name":"Key Laboratory of Viral Heart Diseases Chinese Academy of Medical Sciences  Shanghai 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