整合素调控动脉粥样硬化血管平滑肌细胞表型转化的研究进展

Research Progress on Integrin-Mediated Regulation of Vascular Smooth Muscle Cell Phenotypic Transformation in Atherosclerosis

动脉粥样硬化(atherosclerosis,AS)是一种慢性炎症性血管疾病,也是许多心脑血管疾病的主要病理基础,发病机制复杂且目前尚未完全阐明。血管平滑肌细胞(vascular smooth muscle cell,VSMC)是构成血管壁的主要细胞类型之一,参与调节血管壁的收缩与舒张功能,维持血管张力。然而,在促AS有害因素刺激下,收缩型VSMC可发生表型转化,表现出增殖、迁移、黏附、钙化等特性,可直接导致AS斑块形成或破裂。整合素(integrins)负责协调细胞外基质和细胞骨架之间的跨膜联系,在多种疾病的发生发展中扮演重要角色。整合素在调控VSMC向间充质干细胞、肌成纤维细胞、巨噬细胞、成骨细胞等细胞类型的转分化中也发挥着关键作用,可通过调控VSMC表型转化间接影响AS的发生及进展,具有成为新的AS治疗靶点的潜力。本文综述了VSMC表型转化的分类及整合素在VSMC表型转化中的调控作用的研究进展,以期为AS的早期治疗和干预提供新靶点和新策略。

Atherosclerosis(AS)is a chronic inflammatory vascular disease and the main pathological basis for numerous cardiovascular and cerebrovascular diseases.The pathogenesis of AS is complex and not yet fully elucidated.Vascular smooth muscle cells(VSMCs)are one of the main cell types that constitute the vascular wall.They are involved in regulating the systolic and diastolic functions of the vascular wall and maintaining the vascular tone.However,under the stimulation of AS promoting factors,the phenotypic switch occurs in systolic VSMCs,exhibiting characteristics such as proliferation,migration,adhesion,and calcification,which may directly lead to the formation or rupture of AS plaques.Integrins play a critical role in coordinating the transmembrane connections between the extracellular matrix and cytoskeleton,contributing to pathological processes of various diseases.They also play key roles in regulating the transdifferentiation of VSMCs into mesenchymal stem cells,myofibroblasts,macrophages,osteoblasts,and other cell types.To conclude,integrins can indirectly affect the formation and progression of AS by regulating the phenotypic transformation of VSMC,thereby presenting the potential as a new therapeutic target for AS.In this article,we review the classification of VSMC phenotypic transformation and the regulatory role of integrins in VSMC phenotypic transformation,aiming to provide new targets and strategies for the early treatment and intervention of AS.