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Low level of high density lipoprotein (<jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>) is an independent risk factor for cardiac hypertrophy. This study was designed to evaluate the effect of <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content> on mechanical stress\u2010induced cardiac hypertrophy and autophagy. A 48\u2010hr mechanical stretch and a 4\u2010week transverse aortic constriction were employed to induce cardiomyocyte hypertrophy <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, respectively, prior to the assessment of myocardial autophagy using <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3b\u2010II and beclin\u20101. Our results indicated that <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content> significantly reduced mechanical stretch\u2010induced rise in autophagy as demonstrated by <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3b\u2010II and beclin\u20101. In addition, mechanical stress up\u2010regulated <jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content>1 receptor expression in both cultured cardiomyocytes and in mouse hearts, whereas <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content> significantly suppressed the <jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content>1 receptor. Furthermore, the role of Akt phosphorylation in <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>\u2010mediated action was assessed using <jats:styled-content style=\"fixed-case\">MK<\/jats:styled-content>\u20102206, a selective inhibitor for Akt phosphorylation. Our data further revealed that <jats:styled-content style=\"fixed-case\">MK<\/jats:styled-content>\u20102206 mitigated <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>\u2010induced beneficial responses on cardiac remodelling and autophagy. Taken together, our data revealed that <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content> inhibited mechanical stress\u2010induced cardiac hypertrophy and autophagy through downregulation of <jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content>1 receptor, and <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content> ameliorated cardiac hypertrophy and autophagy <jats:italic>via<\/jats:italic> Akt\u2010dependent mechanism.<\/jats:p>","DOI":"10.1111\/jcmm.12567","type":"journal-article","created":{"date-parts":[[2015,5,6]],"date-time":"2015-05-06T10:36:34Z","timestamp":1430908594000},"page":"1929-1938","source":"Crossref","is-referenced-by-count":43,"title":["High\u2010density lipoprotein inhibits mechanical stress\u2010induced cardiomyocyte autophagy and cardiac hypertrophy through angiotensin II type 1 receptor\u2010mediated <scp>PI<\/scp>3K\/Akt 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