Abstract:Atherosclerosis (As) is a chronic vascular disorder characterized by the accumulation of lipids and the hyperplasia of fibrous tissue within the arterial wall. Exosomes, nanoscale extracellular vesicles, serve as a major conduit for intercellular communication, ferrying bioactive cargoes (e.g., proteins and nucleic acids) that modulate pivotal pathological events in As, including lipid deposition, inflammatory response, and plaque stabilization. Endothelial-to-mesenchymal transition (EndoMT) denotes a phenotypic conversion in which endothelial cells downregulate vascular-specific markers, acquire a mesenchymal signature, and thereby potentiate arterial fibrosis and plaque rupture. Emerging evidence indicates that exosomes orchestrate EndoMT by transmitting activating signals through canonical axes such as transforming growth factor-β (TGF-β ) and Wnt/β-catenin, as well as by delivering transcriptional regulators (e.g., Snail, Twist) that repress endothelial identity genes and activate mesenchymal programs. This article systematically reviews the molecular mechanisms by which exosomes regulate As via modulating EndoMT, focuss on how bioactive molecules carried by exosomes derived from different cell types mediate EndoMT and further affect As. This review is expected to provide new strategies for targed intervention and treatment of atherosclerosis.
