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Rapamycin is an inhibitor of serine\/threonine kinase mammalian target of rapamycin (<jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>) involved in the regulation of autophagy as well as oxidative\/nitrative stress. Here, we demonstrated that rapamycin ameliorates myocardial ischaemia reperfusion injury by rescuing the defective cytoprotective mechanisms in hypertrophic heart. Our results showed that chronic rapamycin treatment markedly reduced the phosphorylated <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content> and ribosomal protein S6 expression, but not Akt in both normal and aortic\u2010banded mice. Moreover, chronic rapamycin treatment significantly mitigated <jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content>\u2010induced autophagy dysfunction demonstrated by prompted Beclin\u20101 activation, elevated <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3\u2010I ratio and increased autophagosome abundance. Most importantly, we found that <jats:styled-content style=\"fixed-case\">MI<\/jats:styled-content>\/R\u2010induced myocardial injury was markedly reduced by rapamycin treatment manifested by the inhibition of myocardial apoptosis, the reduction of myocardial infarct size and the improvement of cardiac function in hypertrophic heart. Mechanically, rapamycin reduced the <jats:styled-content style=\"fixed-case\">MI<\/jats:styled-content>\/R\u2010induced <jats:styled-content style=\"fixed-case\">iNOS<\/jats:styled-content>\/gp91<jats:sup>phox<\/jats:sup> protein expression and decreased the generation of <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> and superoxide, as well as the cytotoxic peroxynitrite. Moreover, rapamycin significantly mitigated <jats:styled-content style=\"fixed-case\">MI<\/jats:styled-content>\/R\u2010induced endoplasmic reticulum stress and mitochondrial impairment demonstrated by reduced Caspase\u201012 activity, inhibited <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> activation, decreased cytoplasmic Cyto\u2010C release and preserved intact mitochondria. In addition, inhibition of <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content> also enhanced the phosphorylated <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content>, and inactivated <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>3\u03b2, a pivotal downstream target of Akt and <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> signallings. Taken together, these results suggest that <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content> signalling protects against <jats:styled-content style=\"fixed-case\">MI<\/jats:styled-content>\/R injury through autophagy induction and <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\u2010mediated antioxidative and anti\u2010nitrative stress in mice with hypertrophic myocardium.<\/jats:p>","DOI":"10.1111\/jcmm.13451","type":"journal-article","created":{"date-parts":[[2018,1,4]],"date-time":"2018-01-04T11:22:09Z","timestamp":1515064929000},"page":"1708-1719","source":"Crossref","is-referenced-by-count":40,"title":["Mammalian target of rapamycin inhibition attenuates myocardial ischaemia\u2013reperfusion injury in hypertrophic heart"],"prefix":"10.1111","volume":"22","author":[{"given":"Lei\u2010Lei","family":"Ma","sequence":"first","affiliation":[{"name":"Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital and Institute of Biomedical 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