Reduction of CTRP9, a novel anti-platelet adipokine, contributes to abnormal platelet activity in diabetic animals.
Reduction of CTRP9, a novel anti-platelet adipokine, contributes to abnormal platelet activity in diabetic animals.
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DOI：
10.1186/s12933-015-0321-1
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发表时间：
2016-01-11
影响因子：
9.3
通讯作者：
Li R
中科院分区：
文献类型：
--
作者：
Wang W;Lau WB;Wang Y;Ma X;Li R
血小板高反应性是加速动脉粥样硬化的一个重要原因，增加了糖尿病患者血栓性血管事件的风险。导致糖尿病期间血小板活性异常的机制是复杂的，并且尚未完全确定。目前的研究试图阐明CTRP 9，一种新的脂联素蛋白，在增强血小板活性中的作用，并确定CTRP 9是否可以抑制血小板活性。成年雄性C57 BL/6 J小鼠随机接受高脂饮食（HFD）或正常饮食（ND）。HFD后8周，处死动物，测定血浆CTRP 9和血小板聚集。HFD喂养的动物显著增加体重增加，并在HFD后8周变得高血糖和高胰岛素血症。与ND动物相比，HFD动物表现出显著降低的血浆CTRP 9浓度和增加的血小板对ADP的反应，表现为增大的聚集幅度、更陡的聚集斜率、更大的曲线下面积和更短的滞后时间（P < 0.01）。观察到血浆CTRP 9浓度与血小板聚集幅度之间的显著负相关。更重要的是，在来自ND和HFD动物的血小板样品中，CTRP 9的体外预处理显著抑制ADP刺激的血小板活化。综上所述，我们的结果表明，糖尿病期间血浆CTRP 9浓度降低在血小板过度活跃中起着致病作用，有助于在这种病理条件下血小板诱导的心血管损伤。增强CTRP 9产生和/或外源性补充CTRP 9可通过抑制异常血小板活性来保护糖尿病心血管损伤。
Platelet hyper-reactivity is a crucial cause of accelerated atherosclerosis increasing risk of thrombotic vascular events in diabetic patients. The mechanisms leading to abnormal platelet activity during diabetes are complex and not fully defined. The current study attempted to clarify the role of CTRP9, a novel adiponectin paralog, in enhanced platelet activity and determined whether CTRP9 may inhibit platelet activity. Adult male C57BL/6 J mice were randomized to receive high-fat diet (HFD) or normal diet (ND). 8 weeks after HFD, animals were sacrificed, and both plasma CTRP9 and platelet aggregation were determined. HFD-fed animals increased weight gain significantly, and became hyperglycemic and hyperinsulinemic 8 weeks post-HFD. Compared to ND animals, HFD animals exhibited significantly decreased plasma CTRP9 concentration and increased platelet response to ADP, evidenced by augmented aggregation amplitude, steeper aggregation slope, larger area under the curve, and shorter lag time (P < 0.01). A significant negative correlation between plasma CTRP9 concentration and platelet aggregation amplitude was observed. More importantly, in vitro pre-treatment with CTRP9 significantly inhibited ADP-stimulated platelet activation in platelet samples from both ND and HFD animals. Taken together, our results suggest reduced plasma CTRP9 concentration during diabetes plays a causative role in platelet hyper-activity, contributing to platelet-induced cardiovascular damage during this pathologic condition. Enhancing CTRP9 production and/or exogenous supplementation of CTRP9 may protect against diabetic cardiovascular injury via inhibition of abnormal platelet activity.