Spermidine-enhanced Autophagic Flux Improves Cardiac Dysfunction Following Myocardial Infarction By Targeting AMPK/mTORs Signaling Pathway

Background and Purpose:Spermidine(SPD),a natural polyamine,is abundant in mammalian cells and is involved in cell growth,proliferation and regeneration.A recent study found that oral SPD supplements exert a cardioprotective effect in aging-related cardiac dysfunction via enhancing autophagic flux.However,the effect of SPD on myocardial injury and cardiac dysfunction following myocardial infarction(MI)remains unknown.Experimental Approach:In vitro and in vivo models of myocardial injury were adopted to determine the role of SPD in MI.Angiotensin ?(Ang ?)was used to induce cultured neonatal rat cardiomyocytes(NRCs)injury and MI model of Sprague-Dawley rats was constructed by permanent ligation of the left anterior descending artery.Key Results:In this study,we found that SPD improved cardiomyocyte viability and decreased cell necrosis in NRCs treated with Ang ?.SPD reduced infarct size and improved cardiac function as well as alleviated myocardial hypertrophy in post-MI rats.Besides,SPD suppressed the oxidative damage and inflammatory cytokines induced by MI.Moreover,SPD enhanced autophagic flux and decreased apoptosis both in vitro and in vivo.Furthermore,we found that the protective effects of SPD on the cardiomyocyte apoptosis and cardiac dysfunction were abolished by autophagy inhibitor chioroquine,indicating that SPD exerted cardioprotective effects at least partially through promoting autophagic flux.We further noted that SPD enhanced autophagic flux by activation of AMPK/mTOR signalling pathway.Conclusion and Implications:Conclusively,our findings suggest for the first time that SPD improves MI-induced cardiac dysfunction by promoting the AMPK/mTOR-mediated autophagic flux.