title: C1q/Tumor Necrosis Factor-Related Protein 9 Protects against Acute Myocardial Injury through an Adiponectin Receptor I-AMPK-Dependent Mechanism.
abstract: Obesity is a risk factor for cardiovascular disease. C1q/tumor necrosis factor-related protein 9 (CTRP9) is an adipokine that is downregulated by obesity. We investigated the role of CTRP9 in cardiac injury with loss-of-function genetic manipulations and defined the receptor-mediated signaling pathway downstream of this adipokine. CTRP9-knockout (CTRP9-KO) mice at the age of 12 weeks were indistinguishable from wild-type (WT) mice under basal conditions. CTRP9-KO mice had exacerbated contractile left ventricle dysfunction following intraperitoneal injection of lipopolysaccharide (LPS) compared to WT mice. Administration of LPS to CTRP9-KO mice also resulted in increased expression of proinflammatory cytokines and oxidative stress markers in the heart compared to WT mice. Likewise, CTRP9-KO mice showed increased myocardial infarct size and elevated expression of inflammatory mediators in ischemic heart following ischemia and reperfusion compared to WT mice. Treatment of cardiac myocytes with CTRP9 protein led to suppression of LPS-induced expression of proinflammatory genes, which was reversed by blockade of AMPK or ablation of adiponectin receptor I (AdipoR1). Systemic delivery of CTRP9 attenuated LPS-induced cardiac dysfunction in WT mice but not in muscle-specific transgenic mice expressing dominant-negative mutant form of AMPK or in AdipoR1-knockout mice. CTRP9 protects against acute cardiac damage in response to pathological stimuli by suppressing inflammatory reactions through AdipoR1/AMPK-dependent mechanisms.
authors: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Takahiro
authors: T
authors: Kambara
authors: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan rshibata@med.nagoya-u.ac.jp nouchi@med.nagoya-u.ac.jp.
authors: Rei
authors: R
authors: Shibata
authors: Molecular Cardiovascular Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Koji
authors: K
authors: Ohashi
authors: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Kazuhiro
authors: K
authors: Matsuo
authors: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Mizuho
authors: M
authors: Hiramatsu-Ito
authors: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Takashi
authors: T
authors: Enomoto
authors: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Daisuke
authors: D
authors: Yuasa
authors: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Masanori
authors: M
authors: Ito
authors: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Satoko
authors: S
authors: Hayakawa
authors: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Hayato
authors: H
authors: Ogawa
authors: Renal Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors: Tamar
authors: T
authors: Aprahamian
authors: Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, USA.
authors: Kenneth
authors: K
authors: Walsh
authors: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Toyoaki
authors: T
authors: Murohara
authors: Molecular Cardiovascular Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan rshibata@med.nagoya-u.ac.jp nouchi@med.nagoya-u.ac.jp.
authors: Noriyuki
authors: N
authors: Ouchi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000276:immunology*; D052242:Adiponectin / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D009206:Myocardium / Q000276:immunology / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000276:immunology / Q000473:pathology; D051381:Rats; D054419:Receptors, Adiponectin / Q000276:immunology*
chemical_list: D052242:Adiponectin; C534692:CTRP9 protein, mouse; D006023:Glycoproteins; D008070:Lipopolysaccharides; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; D055372:AMP-Activated Protein Kinases