C1q/tumor necrosis factor-related protein-3, a newly identified adipokine, is a novel antiapoptotic, proangiogenic, and cardioprotective molecule in the ischemic mouse heart.
BACKGROUND
Obesity and diabetes mellitus adversely affect postischemic heart remodeling via incompletely understood mechanisms. C1q/tumor necrosis factor-related protein-3 (CTRP3) is a newly identified adipokine exerting beneficial metabolic regulation, similar to adiponectin. The aim of the present study was to determine whether CTRP3 may regulate postischemic cardiac remodeling and cardiac dysfunction, and, if so, to elucidate the underlying mechanisms.


RESULTS
Male adult mice were subjected to myocardial infarction (MI) via left anterior descending coronary artery occlusion. Both the effect of MI on endogenous CTRP3 expression/production and the effect of exogenous CTRP3 (adenovirus or recombinant CTRP3) replenishment on MI injury were investigated. MI significantly inhibited adipocyte CTRP3 expression and reduced the plasma CTRP3 level, reaching a nadir 3 days after MI. CTRP3 replenishment improved survival rate (P<0.05), restored cardiac function, attenuated cardiomyocyte apoptosis, increased revascularization, and dramatically reduced interstitial fibrosis (all P<0.01). CTRP3 replenishment had no significant effect on cardiac AMP-activated protein kinase phosphorylation but significantly increased Akt phosphorylation and expression of hypoxia inducing factor-1α and vascular endothelial growth factor. Surprisingly, treatment of human umbilical vascular endothelial cells with CTRP3 did not directly affect nitric oxide production or tube formation. However, preconditioned medium from CTRP3-treated cardiomyocytes significantly enhanced human umbilical vascular endothelial cell tube formation, an effect blocked by either pretreatment of cardiomyocytes with a PI3K inhibitor or pretreatment of human umbilical vascular endothelial cells with a vascular endothelial growth factor inhibitor. Finally, the protective effect of adipocyte-conditioned medium against hypoxia-induced cardiomyocyte injury is significantly blunted when CTRP3 is knocked down.


CONCLUSIONS
CTRP3 is a novel antiapoptotic, proangiogenic, and cardioprotective adipokine, the expression of which is significantly inhibited after MI.
Department of Cardiovascular Surgery, Xijing Hospital, the Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi Province, PR. China, 710032. Yiwei@fmmu.edu.cn
Wei
W
Yi
Yang
Y
Sun
Yuexing
Y
Yuan
Wayne Bond
WB
Lau
Qijun
Q
Zheng
Xiaoliang
X
Wang
Yajing
Y
Wang
Xiying
X
Shang
Erhe
E
Gao
Walter J
WJ
Koch
Xin-Liang
XL
Ma
D054392:Adipokines / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use; D043925:Angiogenesis Inducing Agents / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000378:metabolism / Q000627:therapeutic use*; D055785:Gene Knockdown Techniques / Q000379:methods; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D011897:Random Allocation
D054392:Adipokines; D043925:Angiogenesis Inducing Agents; D051017:Apoptosis Regulatory Proteins; C428135:CORS26 protein, mouse; D002316:Cardiotonic Agents