C1q/tumor necrosis factor-related protein-3, a newly identified adipokine, is a novel antiapoptotic, proangiogenic, and cardioprotective molecule in the ischemic mouse heart.
C1q/tumor necrosis factor-related protein-3, a newly identified adipokine, is a novel antiapoptotic, proangiogenic, and cardioprotective molecule in the ischemic mouse heart.
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C1q/肿瘤坏死因子相关蛋白-3 是一种新鉴定的脂肪因子，是缺血小鼠心脏中的一种新型抗凋亡、促血管生成和心脏保护分子
DOI：
10.1161/circulationaha.112.099937
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发表时间：
2012-06-26
期刊：
影响因子：
37.8
通讯作者：
Ma XL
中科院分区：
文献类型：
--
作者：
Yi W;Sun Y;Yuan Y;Lau WB;Zheng Q;Wang X;Wang Y;Shang X;Gao E;Koch WJ;Ma XL
肥胖/糖尿病通过不完全理解的潜在机制对缺血后心脏重塑产生不利影响。C1 q/TNF相关蛋白3（C1 q/TNF-related protein-3，CTRP 3）是一种新发现的脂肪因子，具有与脂联素相似的代谢调节作用。目前的研究确定CTRP 3是否可以调节缺血后心脏重塑和心功能不全，如果是这样，试图阐明所涉及的潜在机制。雄性成年小鼠通过左前降支（LAD）冠状动脉闭塞进行心肌梗死（MI）。研究了MI对内源性CTRP 3表达/产生的影响和外源性CTRP 3（腺病毒或重组CTRP 3）补充对MI损伤的影响。MI显著抑制脂肪细胞CTRP 3表达并降低血浆CTRP 3水平，MI后3天达到最低值。补充CTRP 3可提高存活率（P<0.05），恢复心功能，减少心肌细胞凋亡，增加血管重建，并显著减少间质纤维化（P值均<0.01）。补充CTRP 3对心脏AMP活化蛋白激酶（AMPK）磷酸化没有显著影响，但显著增加Akt磷酸化以及缺氧诱导因子-1 α（HIF-1α）和血管内皮生长因子（VEGF）的表达。令人惊讶的是，用CTRP 3处理人脐血管内皮细胞（HUVEC）并不直接影响NO产生或管形成。然而，来自CTRP 3处理的心肌细胞的预处理培养基显著增强HUVEC管形成，这一作用被用PI 3 K抑制剂预处理心肌细胞或用VEGF抑制剂预处理HUVEC阻断。最后，来自CTRP 3敲低的3 T3细胞的预条件培养基显著增强缺氧诱导的心肌细胞损伤。CTRP 3是一种新的抗凋亡、促血管生成和心脏保护性脂肪因子，其表达在MI后被显著抑制。
Obesity/diabetes adversely affects post-ischemic heart remodeling via incompletely understood underlying mechanisms. C1q/TNF-related protein-3 (CTRP3) is a newly identified adipokine exerting beneficial metabolic regulation, similar to adiponectin. The current study determined whether CTRP3 may regulate post-ischemic cardiac remodeling and cardiac dysfunction, and, if so, sought to elucidate the involved underlying mechanisms. Male adult mice were subjected to myocardial infarction (MI) via left anterior descending (LAD) coronary artery occlusion. Both the effect of MI upon endogenous CTRP3 expression/production and the effect of exogenous CTRP3 (adenovirus or recombinant CTRP3) replenishment upon MI injury were investigated. MI significantly inhibited adipocyte CTRP3 expression and reduced plasma CTRP3 level, reaching nadir 3 days post-MI. CTRP3 replenishment improved survival rate (P<0.05), restored cardiac function, attenuated cardiomyocyte apoptosis, increased revascularization, and dramatically reduced interstitial fibrosis (P values all <0.01). CTRP3 replenishment had no significant effect upon cardiac AMP-activated protein kinase (AMPK) phosphorylation, but significantly increased Akt phosphorylation and expression of hypoxia inducing factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). Surprisingly, treatment of human umbilical vascular endothelial cells (HUVECs) with CTRP3 did not directly affect NO production or tube formation. However, pre-conditioned medium from CTRP3-treated cardiomyocytes significantly enhanced HUVEC tube formation, an effect blocked by either pre-treatment of cardiomyocytes with a PI3K inhibitor, or pre-treatment of HUVECs with a VEGF inhibitor. Finally, pre-conditioned medium from CTRP3-knockdown 3T3 cells significantly enhanced hypoxia-induced cardiomyocyte injury. CTRP3 is a novel anti-apoptotic, pro-angiogenic, and cardioprotective adipokine, whose expression is significantly inhibited following MI.