title: C1q/TNF-related protein-1 functions to protect against acute ischemic injury in the heart.
abstract: Obesity is associated with an increased risk of cardiovascular disease. C1q/TNF-related protein (CTRP)-1 is a poorly characterized adipokine that is up-regulated in association with ischemic heart disease. We investigated the role of CTRP1 in myocardial ischemia injury. CTRP1-knockout mice showed increased myocardial infarct size, cardiomyocyte apoptosis, and proinflammatory gene expression after I/R compared with wild-type (WT) mice. In contrast, systemic delivery of CTRP1 attenuated myocardial damage after I/R in WT mice. Treatment of cardiomyocytes with CTRP1 led to reduction of hypoxia-reoxygenation-induced apoptosis and lipopolysaccharide-stimulated expression of proinflammatory cytokines, which was reversed by inhibition of sphingosine-1-phosphate (S1P) signaling. Treatment of cardiomyocytes with CTRP1 also resulted in the increased production of cAMP, which was blocked by suppression of S1P signaling. The antiapoptotic and anti-inflammatory actions of CTRP1 were cancelled by inhibition of adenylyl cyclase or knockdown of adiponectin receptor 1. Furthermore, blockade of S1P signaling reversed CTRP1-mediated inhibition of myocardial infarct size, apoptosis, and inflammation after I/R in vivo. These data indicate that CTRP1 protects against myocardial ischemic injury by reducing apoptosis and inflammatory response through activation of the S1P/cAMP signaling pathways in cardiomyocytes, suggesting that CTRP1 plays a crucial role in the pathogenesis of ischemic heart disease.
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yuasa
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Shibata
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Mizutani
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kataoka
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kambara
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Uemura
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Kanemura
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Hayakawa
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Hiramatsu-Ito
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ito
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Murate
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.affiliation: *Department of Cardiology, Department of Molecular Cardiovascular Medicine, and Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; and College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan nouchi@med.nagoya-u.ac.jp ohashik@med.nagoya-u.ac.jp.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology*; D007249:Inflammation / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D020011:Protective Agents / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D054392:Adipokines; C570300:CTRP1 protein, mouse; D016207:Cytokines; D008246:Lysophospholipids; D020011:Protective Agents; C060506:sphingosine 1-phosphate; D000242:Cyclic AMP; D013110:Sphingosine
keywords: CTRP1; adipokine; apoptosis; inflammation; ischemia–reperfusion injury