固有免疫介导的炎症反应在动脉粥样硬化发病机制中的研究进展

动脉粥样硬化是常见慢性心脑血管疾病的病理基础,其病变始于血管内皮细胞构成的天然屏障功能障碍,由各种损伤因子影响内皮细胞Caspase-1/Sirt1/AP-1、SREBP2/NOX2/NLRP3、KLF2/FoxP1/NLRP3、NFAT5/NLRP3等通路信号转导、相关炎症基因表达,激活内皮细胞,继而单核细胞浸润主动脉壁内膜下并分化为巨噬细胞,引起相应内皮激活的固有免疫反应,在NLRP3/ASC/Caspase-1炎性小体途径激活后,使促炎症细胞因子IL-1β、IL-18释放增加,介导下游炎症因子、趋化因子等表达增加,促进动脉粥样硬化炎症反应;血管壁持续慢性炎症反应使血管平滑肌细胞表型转变,促进动脉粥样硬化斑块形成,还使斑块成分发生改变、易损性增加,斑块微钙化则增加了斑块处血管应力,破裂危险增加。本文综述了固有免疫介导的动脉粥样硬化炎症机制研究现状,为动脉粥样硬化抗炎药物研发提供思路以及促进抗动脉粥样硬化研究的实验设计。

Research progress of innate immune mediated inflammatory response in pathogenesis of atherosclerosis

Atherosclerosis(As)is the pathological basis of a variety of common chronic cardiovascular and cerebrovascular diseases,which begins with the destruction of the natural barrier formed by the vascular endothelial cells.The main manifestations can change the signal transduction and related inflammatory gene expression of Caspase-1/Sirt1/AP-1,SREBP2/NOX2/NLRP3,KLF2/FoxP1/NLRP3,NFAT5/NLRP3 and thus activating endothelial cells.Then,monocytes infiltrate into the intima of aortic wall and differentiate into macrophages,resulting in an innate immune response in response to endothelial activation.Firstly,cholesterol crystallization in macrophages activates NLRP3/ASC/Caspase-1 inflammatory body pathway under the synergistic effect of other regulatory signals.It can increase the release of pro-inflammatory cytokines IL-1β and IL-18,mediate the expression of downstream inflammatory factors and chemokines,and promote the inflammatory response of As.Sustained chronic inflammatory reaction in vascular wall can change the phenotype of vascular smooth muscle cells,promote the formation of as plaque,change the composition of plaque and increase the vulnerability.Plaque microcalcification also increases the vascular stress at the plaque,with consequences that the risk of rupture is increased.In this paper,the research status of inflammatory mechanism of As,mediated by innate immune,can provide ideas for the development of anti-inflammatory drugs and promote the experimental design of anti-inflammatory research.