Department of Internal Medicine and CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, PO Box 616, Maastricht 6200, MD, The Netherlands.
Department of Internal Medicine and CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, PO Box 616, Maastricht 6200, MD, The Netherlands.
Mol Immunol. 2014 Oct;61(2):135-48. doi: 10.1016/j.molimm.2014.06.031. Epub 2014 Jul 10.
The complement system has been implicated in obesity, fatty liver, diabetes and cardiovascular disease (CVD). Complement factors are produced in adipose tissue and appear to be involved in adipose tissue metabolism and local inflammation. Thereby complement links adipose tissue inflammation to systemic metabolic derangements, such as low-grade inflammation, insulin resistance and dyslipidaemia. Furthermore, complement has been implicated in pathophysiological mechanisms of diet- and alcohol induced liver damage, hyperglycaemia, endothelial dysfunction, atherosclerosis and fibrinolysis. In this review, we summarize current evidence on the role of the complement system in several processes of human cardiometabolic disease. C3 is the central component in complement activation, and has most widely been studied in humans. C3 concentrations are associated with insulin resistance, liver dysfunction, risk of the metabolic syndrome, type 2 diabetes and CVD. C3 can be activated by the classical, the lectin and the alternative pathway of complement activation; and downstream activation of C3 activates the terminal pathway. Complement may also be activated via extrinsic proteases of the coagulation, fibrinolysis and the kinin systems. Studies on the different complement activation pathways in human cardiometabolic disease are limited, but available evidence suggests that they may have distinct roles in processes underlying cardiometabolic disease. The lectin pathway appeared beneficial in some studies on type 2 diabetes and CVD, while factors of the classical and the alternative pathway were related to unfavourable cardiometabolic traits. The terminal complement pathway was also implicated in insulin resistance and liver disease, and appears to have a prominent role in acute and advanced CVD. The available human data suggest a complex and potentially causal role for the complement system in human cardiometabolic disease. Further, preferably longitudinal studies are needed to disentangle which aspects of the complement system and complement activation affect the different processes in human cardiometabolic disease.
补体系统与肥胖、脂肪肝、糖尿病和心血管疾病（CVD）有关。补体因子在脂肪组织中产生，似乎参与脂肪组织代谢和局部炎症。因此，补体将脂肪组织炎症与全身代谢紊乱联系起来，如低度炎症、胰岛素抵抗和血脂异常。此外，补体还与饮食和酒精引起的肝损伤、高血糖、内皮功能障碍、动脉粥样硬化和纤维蛋白溶解的病理生理机制有关。在这篇综述中，我们总结了补体系统在几种人类心血管代谢疾病过程中的作用的现有证据。C3 是补体激活的核心成分，在人类中研究得最为广泛。C3 浓度与胰岛素抵抗、肝功能障碍、代谢综合征风险、2 型糖尿病和 CVD 相关。C3 可被补体经典途径、凝集素途径和替代途径激活；C3 的下游激活激活末端途径。补体也可通过凝血、纤维蛋白溶解和激肽系统的外在蛋白酶激活。关于人类心血管代谢疾病中不同补体激活途径的研究有限，但现有证据表明，它们在心血管代谢疾病的潜在机制中可能具有不同的作用。凝集素途径在一些 2 型糖尿病和 CVD 研究中似乎有益，而经典途径和替代途径的因子与不良的心血管代谢特征相关。末端补体途径也与胰岛素抵抗和肝病有关，并且在急性和晚期 CVD 中似乎具有突出作用。现有的人类数据表明，补体系统在人类心血管代谢疾病中具有复杂且潜在的因果作用。此外，需要进行更好的纵向研究，以厘清补体系统和补体激活的哪些方面影响人类心血管代谢疾病的不同过程。
