Extracellular vesicles in vascular diseases: pathological mechanisms and therapeutic application progress

Abstract

Vascular diseases-including atherosclerosis, essential hypertension, pulmonary arterial hypertension, aortic dissection, and aneurysms-share core pathological mechanisms including endothelial dysfunction, inflammation-oxidative stress cascades, and aberrant activation of vascular smooth muscle cells (VSMCs). This review focuses on these four disorders as classic case studies to elucidate the multifaceted roles of extracellular vesicles (EVs) in vascular pathophysiology. Emerging evidence highlights that autoimmune-mediated vascular wall injury exacerbates these common pathogenic pathways in a subset of patients. EVs, nanoscale mediators endogenously produced by cells, are increasingly recognized for their multifaceted roles in vascular pathophysiology. They act not only as carriers of pathological signals [e.g., proteins such as cytokines, autoantigens, and proteases, as well as nucleic acids such as microRNAs (miRNAs)], but also as regulators of immune homeostasis. Beyond their well-documented function as miRNA transporters, EVs are now understood to serve as critical shuttles for functional proteins, including cytokines, growth factors, proteases, and even functional receptors. These cargoes can directly activate signaling pathways in recipient cells, thereby driving both vascular pathogenesis and repair processes. Furthermore, EVs also hold innovative platforms for targeted therapeutic delivery. This review examines the mechanistic roles of EVs in vascular disease therapy, explores current engineering strategies to enhance their therapeutic potential, and discusses the challenges and future prospects of their clinical translation.

Keywords

Extracellular vesicles / vascular diseases / atherosclerosis / hypertension / vascular inflammation / endothelial repair / therapeutic applications

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