Complement C3: an emerging risk factor in cardiometabolic disease.
Complement C3: an emerging risk factor in cardiometabolic disease.
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DOI：
10.1007/s00125-012-2462-z
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发表时间：
2012-04
期刊：
影响因子：
8.2
通讯作者：
Stehouwer, C. D. A.
中科院分区：
文献类型：
--
作者：
Hertle, E.;van Greevenbroek, M. M. J.;Stehouwer, C. D. A.
关键词：
C3是补体系统的中心成分，通过三种主要活化途径-经典途径、凝集素途径和旁路途径-中的任何一种活化C3导致末端补体途径的启动和过敏毒素C3 a的释放。C3 a及其失活产物C3 a-desarg分别通过C3 a受体和C5 a样受体2的终末途径激活和信号传导可诱导炎症、免疫调节和代谢反应。C3与代谢紊乱有关，特别是肥胖、血脂异常、胰岛素抵抗、肝功能障碍和糖尿病，C3越来越被认为是一种心脏代谢风险因素。C3可能在糖尿病的大血管和微血管并发症中发挥作用。此外，C3可能与凝血系统相互作用，因此也有助于促凝血、纤溶功能减退，最终导致血栓形成前状态。最近的数据表明，C3与纤维蛋白凝块的结合具有糖尿病依赖性，并伴随着对凝块特性的影响。总而言之，流行病学和实验证据一致表明补体C3在代谢、动脉粥样硬化/动脉粥样硬化血栓形成和微血管病过程中的作用，进一步的研究应致力于阐明心脏代谢疾病中的补体功能和激活。
C3 is the central component of the complement system and activation of C3 via any of the three major activation pathways—the classical, the lectin and the alternative pathways—results in initiation of the terminal complement pathway and release of the anaphylatoxin C3a. Both terminal pathway activation and signalling of C3a and its inactivation product C3a-desarg via the C3a receptor and C5a-like receptor 2, respectively, can induce inflammatory, immunomodulatory and metabolic responses. C3 has been implicated in metabolic disorders, notably adiposity, dyslipidaemia, insulin resistance, liver dysfunction and diabetes, and C3 is increasingly recognised as a cardiometabolic risk factor. C3 may play a role in the macrovascular, as well as microvascular, complications of diabetes. Moreover, C3 may interact with the coagulation system and as such also contribute to a procoagulant, hypofibrinolytic and, ultimately, prothrombotic state. Recent data suggest a diabetes-dependent incorporation of C3 into fibrin clots, with concomitant effects on clot characteristics. Taken together, epidemiological and experimental evidence concordantly point to a role of complement C3 in metabolic, atherosclerotic/atherothrombotic and microangiopathic processes and further research should be directed towards the elucidation of complement function and activation in cardiometabolic disorders.
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