title: CTRP9 protein protects against myocardial injury following ischemia-reperfusion through AMP-activated protein kinase (AMPK)-dependent mechanism.
abstract: Ischemic heart disease is the major cause of death in Western countries. CTRP9 (C1q/TNF-related protein 9) is a fat-derived plasma protein that has salutary effects on glucose metabolism and vascular function. However, the functional role of CTRP9 in ischemic heart disease has not been clarified. Here, we examined the regulation of CTRP9 in response to acute cardiac injury and investigated whether CTRP9 modulates cardiac damage after ischemia and reperfusion. Myocardial ischemia-reperfusion injury resulted in reduced plasma CTRP9 levels and increased plasma free fatty acid levels, which were accompanied by a decrease in CTRP9 expression and an increase in NADPH oxidase component expression in fat tissue. Treatment of cultured adipocytes with palmitic acid or hydrogen peroxide reduced CTRP9 expression. Systemic administration of CTRP9 to wild-type mice, before the induction of ischemia or at the time of reperfusion, led to a reduction in myocardial infarct size following ischemia-reperfusion. Administration of CTRP9 also attenuated myocyte apoptosis in ischemic heart, which was accompanied by increased phosphorylation of AMP-activated protein kinase (AMPK). Treatment of cardiac myocytes with CTRP9 protein reduced apoptosis in response to hypoxia/reoxygenation and stimulated AMPK phosphorylation. Blockade of AMPK activity reversed the suppressive actions of CTRP9 on cardiomyocyte apoptosis. Knockdown of adiponectin receptor 1 diminished CTRP9-induced increases in AMPK phosphorylation and survival of cardiac myocytes. Our data suggest that CTRP9 protects against acute cardiac injury following ischemia-reperfusion via an AMPK-dependent mechanism.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kambara
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.forename: Rei
authors.initials: R
authors.lastname: Shibata
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogura
authors.forename: Sonomi
authors.initials: S
authors.lastname: Maruyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Enomoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Uemura
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yuasa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Megumi
authors.initials: M
authors.lastname: Miyabe
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kataoka
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D052242:Adiponectin / Q000097:blood* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000097:blood* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D019308:Palmitic Acid / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats
chemical_list: D052242:Adiponectin; C534692:CTRP9 protein, mouse; D005230:Fatty Acids, Nonesterified; D006023:Glycoproteins; D019308:Palmitic Acid; D055372:AMP-Activated Protein Kinases