The Role of Extracellular Vesicle–Derived miRNA in the Atherosclerotic Burden

In the context of atheroma-related sequelae, the role of extracellular vesicles (EVs) continues to spike interest. Their ability to traffic molecular cargo between cells highlights their role in intercellular communication, and consequently their involvement in mediating molecular events at the basis of physiological and pathologic processes. EVs encapsulate miRNAs within their lumen, shielding them from circulating ribonucleases, which would otherwise catalyze their degradation. However, there is an ongoing debate regarding the implication of miRNA contained within EVs in modulating biological activities on a molecular level. Therefore, the aim of the present review is to discuss the role of EV-derived miRNA, focusing on their implication in molecular mechanisms underlying atheroma formation. EVs of endothelial origin can regulate monocyte activation by transferring miR-10a that targets components of the inflammatory pathway. Tail vein administration of EVs derived from endothelial cells enriched in miR-34c-5p markedly reduces atherosclerosis progression. In patients with stable coronary artery disease, elevated levels of miR-126 and miR-199a in circulating EVs are significantly associated with a reduced incidence of major adverse cardiovascular event rate. These nanoparticles, released by all cells into most biological fluids, hold promise as a liquid biopsy tool as their circulating patterns and cargo can reflect the onset and severity of cardiovascular diseases. © 2025 American Society for Investigative Pathology.