Vascular and Immune Cell Interactions in Atherosclerosis: Mechanisms, Plaque Destabilization, and Therapeutic Opportunities

Atherosclerosis (AS) is a progressive vascular disease characterized by lipid accumulation within the arterial intima, chronic inflammation, and plaque formation. It represents the underlying pathological basis of major cardiovascular and cerebrovascular events, including coronary artery disease, acute myocardial infarction, and ischemic stroke. Accumulating evidence suggests that the initiation and progression of AS are not driven by dysfunction of a single cell type but rather result from complex and dynamic interactions among multiple vascular resident and immune cells, including endothelial cells (ECs), vascular smooth muscle cells (VSMCs), macrophages, and lymphocytes. This review systematically summarizes the functional and phenotypic characteristics of these four major cell types in atherosclerotic lesions, with particular emphasis on their bidirectional regulatory networks. We provide an in-depth analysis of key intercellular communication mechanisms, including paracrine signaling, exosome-mediated transfer, oxidative stress crosstalk, and autophagy regulation, all of which play central roles in plaque microenvironment remodeling, lipid core expansion, fibrous cap degradation, and plaque destabilization. Furthermore, we highlight recent advances in translational strategies targeting cell–cell interactions, focusing on the mechanisms of action and clinical potential of representative agents.