Department of Cardiovascular Surgery, Xijing Hospital, the Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi Province, PR. China, 710032.
Circulation. 2012 Jun 26;125(25):3159-69. doi: 10.1161/CIRCULATIONAHA.112.099937. Epub 2012 May 31.
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.
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.
CTRP3 is a novel antiapoptotic, proangiogenic, and cardioprotective adipokine, the expression of which is significantly inhibited after MI.
肥胖和糖尿病通过尚未完全阐明的机制对缺血后心脏重构产生不利影响。C1q/肿瘤坏死因子相关蛋白-3（CTRP3）是一种新发现的脂肪因子，具有类似于脂联素的有益代谢调节作用。本研究旨在确定 CTRP3 是否可以调节缺血后心脏重构和心功能障碍，如果可以，阐明其潜在机制。
雄性成年小鼠通过左前降支冠状动脉结扎术发生心肌梗死（MI）。研究了 MI 对内源性 CTRP3 表达/产生的影响，以及外源性 CTRP3（腺病毒或重组 CTRP3）补充对 MI 损伤的影响。MI 显著抑制脂肪细胞 CTRP3 的表达，降低血浆 CTRP3 水平，在 MI 后 3 天达到最低点。CTRP3 补充可提高生存率（P<0.05），改善心功能，减少心肌细胞凋亡，增加血管生成，显著减少间质纤维化（均 P<0.01）。CTRP3 补充对心脏 AMP 激活蛋白激酶磷酸化无明显影响，但显著增加 Akt 磷酸化和缺氧诱导因子-1α和血管内皮生长因子的表达。令人惊讶的是，CTRP3 处理的人脐静脉内皮细胞对一氧化氮产生或管形成没有直接影响。然而，CTRP3 处理的心肌细胞的预处理培养基显著增强了人脐静脉内皮细胞的管形成，该作用被心肌细胞的 PI3K 抑制剂预处理或人脐静脉内皮细胞的血管内皮生长因子抑制剂预处理所阻断。最后，当脂肪细胞条件培养基中的 CTRP3 被敲低时，其对缺氧诱导的心肌细胞损伤的保护作用明显减弱。
CTRP3 是一种新型的抗凋亡、促血管生成和心脏保护的脂肪因子，其表达在 MI 后明显受到抑制。
