Vascular Research Lab, IIS-Fundación Jiménez Díaz, Universidad Autonoma de Madrid, and CIBERCV, Spain.
Vascular Research Lab, IIS-Fundación Jiménez Díaz, Universidad Autonoma de Madrid, and CIBERCV, Spain.
Mol Immunol. 2019 Oct;114:207-215. doi: 10.1016/j.molimm.2019.06.016. Epub 2019 Aug 1.
Cardiovascular diseases (CVD) remain the major cause of morbidity and mortality in Europe. The clinical complications associated to arterial wall rupture involve intimal cap rupture in complicated atherosclerotic plaques and medial rupture in abdominal aortic aneurysm (AAA). The mechanisms underlying pathological vascular remodeling include lipid accumulation, cell proliferation, redox imbalance, proteolysis, leukocyte infiltration, cell death, and eventually, thrombosis. The complement system could participate in vascular remodeling by several mechanisms, from an initial protective response that aims in the clearing of cell debris to a potential deleterious role participating in leukocyte chemotaxis and cell activation and bridging innate and adaptive immunity. We have reviewed the presence and distribution of complement components, as well as the triggers of complement activation in atherosclerotic plaques and AAA, to later assess the functional consequences of complement modulation in experimental models of pathological vascular remodeling and the potential role of complement components as potential circulating biomarkers of CVD. On the whole, complement system is a key mechanism involved in vascular remodelling, which could be useful in the diagnostic/prognostic setting, as well as a potential therapeutic target, of CVD.
心血管疾病(CVD)仍然是欧洲发病率和死亡率的主要原因。与动脉壁破裂相关的临床并发症包括复杂粥样斑块中的内膜帽破裂和腹主动脉瘤(AAA)中的中膜破裂。病理性血管重塑的机制包括脂质积累、细胞增殖、氧化还原失衡、蛋白水解、白细胞浸润、细胞死亡,最终导致血栓形成。补体系统可以通过几种机制参与血管重塑,从最初旨在清除细胞碎片的保护反应到参与白细胞趋化和细胞激活以及桥接先天和适应性免疫的潜在有害作用。我们回顾了补体成分在动脉粥样硬化斑块和 AAA 中的存在和分布,以及补体激活的触发因素,以评估补体调节在病理性血管重塑实验模型中的功能后果,以及补体成分作为 CVD 潜在循环生物标志物的潜在作用。总的来说,补体系统是参与血管重塑的关键机制,它在 CVD 的诊断/预后中可能有用,也是一个潜在的治疗靶点。