Cardiovascular diseases are the leading cause of death globally, and atherosclerosis is the major contributor to the development and progression of cardiovascular diseases. Immune responses have a central role in the pathogenesis of atherosclerosis, with the complement system being an acknowledged contributor. Chronic activation of liver-derived and serum-circulating canonical complement sustains endothelial inflammation and innate immune cell activation, and deposition of complement activation fragments on inflamed endothelial cells is a hallmark of atherosclerotic plaques. However, increasing evidence indicates that liver-independent, cell-autonomous and non-canonical complement activities are underappreciated contributors to atherosclerosis. Furthermore, complement activation can also have atheroprotective properties. These specific detrimental or beneficial contributions of the complement system to the pathogenesis of atherosclerosis are dictated by the location of complement activation and engagement of its canonical versus non-canonical functions in a temporal fashion during atherosclerosis progression. In this Review, we summarize the classical and the emerging non-classical roles of the complement system in the pathogenesis of atherosclerosis and discuss potential strategies for therapeutic modulation of complement for the prevention and treatment of atherosclerotic cardiovascular disease.

心血管疾病是全球死亡的主要原因，动脉粥样硬化是导致心血管疾病发展和进展的主要因素。免疫反应在动脉粥样硬化的发病机制中起着核心作用，补体系统是公认的贡献者。肝源性和血清循环经典补体的慢性激活维持了内皮炎症和先天免疫细胞活化，补体激活片段沉积在发炎的内皮细胞上是动脉粥样硬化斑块的标志。然而，越来越多的证据表明，肝脏非依赖性、细胞自主和非经典补体活性是动脉粥样硬化的促成因素被低估。此外，补体激活也可以具有动脉粥样硬化保护特性。补体系统对动脉粥样硬化发病机制的这些特定的有害或有益贡献取决于补体激活的位置以及在动脉粥样硬化进展过程中其经典与非经典功能的参与。在本综述中，我们总结了补体系统在动脉粥样硬化发病机制中的经典和新兴非经典作用，并讨论了补体治疗调节预防和治疗动脉粥样硬化性心血管疾病的潜在策略。