アテローム性動脈硬化症におけるGタンパク質共役受容体シグナル伝達：メカニズムの洞察と治療標的

Atherosclerosis (AS), the primary pathological basis of cardiovascular diseases, is driven by lipid deposition, chronic inflammation, and vascular wall fibrosis. Nevertheless, persistent inflammatory environments and plaque instability remain significant clinical challenges. G protein-coupled receptors (GPCRs), constituting the largest family of membrane receptors in humans, play a central role in AS progression by modulating macrophage polarization, vascular smooth muscle cells (VSMCs) proliferation and migration, and oxidized low-density lipoprotein (ox-LDL) metabolism. Macrophage polarization dictates the inflammatory microenvironment within plaques; GPCRs modulate macrophage phenotypes through downstream signaling pathways, thereby exacerbating or mitigating inflammation. Furthermore, GPCRs regulate VSMCs phenotypic switching, critically influencing the stability of the plaque fibrous cap. Additionally, the interplay between GPCRs and ox-LDL exacerbates endothelial dysfunction and amplifies inflammatory signaling. This review comprehensively summarizes the roles of GPCR family members in AS pathogenesis and explores targeting these molecules as a promising therapeutic strategy for AS, thus highlighting their potential for multi-targeted intervention.