C1q/Tumor Necrosis Factor–Related Protein-9, a Novel Adipocyte-Derived Cytokine, Attenuates Adverse Remodeling in the Ischemic Mouse Heart via Protein Kinase A Activation

• DOI: 10.1161/circulationaha.112.000010
• Publication Date: 2013-09-12T21:37:10Z
• Authors: Yang Sun; Wei Yi; Yuexing Yuan; Wayne Bond Lau; Dinghua Yi; Xiaoliang Wang; Yajing Wang; Hui Su; Xiaoming Wang; Erhe Gao; Walter J. Koch; Xin-Liang Ma
• Keywords: Ventricular remodeling

Background— C1q/tumor necrosis factor–related protein-9 (CTRP9) is a newly identified adiponectin paralog with established metabolic regulatory properties. However, the role of CTRP9 in postmyocardial infarction remodeling remains completely unknown. This study determined whether may regulate cardiac after acute myocardial (AMI) and elucidated underlying mechanisms. Methods Results— Male adult mice were subject to AMI by left anterior descending coronary artery ligation or sham surgery treated saline (vehicle) globular via peritoneal implant osmotic pumps for 6 weeks. H9C2 cell lines used vitro determining Adipocyte expression plasma levels both significantly reduced AMI. Compared vehicle, treatment improved animal survival rate ( P <0.05), restored function attenuated adverse <0.01), ameliorated cardiomyocyte apoptosis fibrosis <0.01). Among multiple antiremodeling molecules determined, AMP-activated protein kinase, kinase A (PKA), Akt activated CTRP9-treated heart. Surprisingly, cardioprotective cardiomyocyte-specific overexpression mutant α2 subunit (AMPK-DN). Additional experiments demonstrated that administration either PKA inhibitor PKA-specific small interfering RNA virtually abolished antiapoptotic effect whereas inhibition less effective blocking cardioprotection. Finally, phosphorylates BCL-2-associated agonist death at its sites, an blocked inhibitor. Conclusions— We demonstrate adipokine attenuates AMI, largely PKA-dependent pathway.