调控动脉粥样硬化泡沫细胞形成的信号通路研究进展

Research progress of pivotal signaling pathways governing foam cell formation during atherosclerosis

动脉粥样硬化作为心脑血管系统中常见的慢性炎症疾病,是冠心病和脑卒中等心血管疾病的主要诱因,多发于血脂异常、高血压和吸烟等群体,早期症状不明显且预后较差。在动脉粥样硬化发病过程中,源于单核巨噬细胞和血管壁平滑肌细胞的泡沫细胞形成和积累是病变发展的标志性事件,研究调控泡沫细胞形成的分子机制对于阐明动脉粥样硬化发病机制以及发现治疗可用的新靶点意义重大。脂质代谢紊乱、脂噬功能障碍、炎症反应以及细胞凋亡异常是影响细胞泡沫化的常见机制,但这些细胞应答上游的信号通路调控网络仍不明晰。本文基于信号通路调控回顾了泡沫细胞的生成过程及其调控机制,总结了PI3K/AKT、MAPK、AMPK、NF-κB、PPARγ/LXRα等信号通路在泡沫化过程中对于脂质代谢、脂噬、炎症以及细胞凋亡等过程的促进或抑制作用,明确了上游信号通路和下游细胞应答间的作用关系,同时概括了可通过调控以上信号通路影响泡沫细胞形成从而抗动脉粥样硬化的潜在药用成分,在构建泡沫细胞形成过程中分子调控网络的同时,也为动脉粥样硬化的临床治疗研究提供了理论依据。

Atherosclerosis is a prevalent chronic inflammatory disease seen in the cardiovascular and cerebrovascular systems,and acts as the primary cause of cardiovascular diseases such as coronary heart disease and stroke.This disease turns to occur in population carrying dyslipidemia,hypertension,and smoking habits.Early symptoms are not obvious and the prognosis is poor.In the pathogenesis of atherosclerosis,the formation and accumulation of foam cells derived from mononuclear macrophages and vascular wall smooth muscle cells are crucial for lesion development.Investigating the molecular mechanisms that regulate foam cell formation holds significant importance in understanding atherosclerosis pathogenesis and identifying new treatment targets.Lipid metabolic disorders,lipid phagocytosis dysfunction,inflammatory responses,and abnormal cell apoptosis are listed as common reasons which promote cell foaming.However,the upstream regulatory signaling network controlling these cellular responses remains to be unclear.This article reviews pivotal signaling pathways which play crucial roles in foam cell formation and their detailed mechanisms,mostly by summarizing the promoting or inhibiting effect of pathways including PI3K/AKT,MAPK,AMPK,NF-κB and PPARγ/LXRαon lipid metabolism,lipid phagocytosis,inflammatory responses and cell apoptosis,and thus illustrated the interaction between upstream signaling ways and downstream cellular responses.Meanwhile,a list of potential pharmaceutical ingredients which display anti-atherosclerosis effects by affecting above signaling pathways during foam cell formation is summed up.Overall,this review provides a summary of the upstream and downstream effects and interactions of various signaling pathways involved in the generation of foam cells,with the hope of constructing a molecular regulatory network during foam cell formation,and providing a theoretical basis for clinical treatment of atherosclerosis.