Figure 2: Detrimental Effects of Extracellular Vesicles on Vascular Function

The functional effect of EVs in cardiovascular disease is extremely complex and depends on the cellular origin, the functional state of the releasing cells, the biological content, the distinct recipient cell, and the transfer capacity of intravesicular functional bioactive molecules. Here, we illustrate the role of EVs as active promoters of endothelial dysfunction, vascular calcification, atherogenesis, plaque instability and thrombosis. Endothelial EVs impair vasorelaxation through local oxidative stress or through increased NADPH oxidase activity. EVs released by erythrocytes react with and degrade NO, EVs from platelet and atherosclerotic plaque induce endothelial apoptosis, both mediating endothelial dysfunction. Monocyte-derived EVs transfer inflammatory miRNAs into endothelial cells inducing vascular inflammation. Vascular smooth muscle cell-derived EVs act as mediators of vascular calcification modulating atherogenesis. EVs isolated from atherosclerotic plaques transfer ICAM-1 to endothelial cells and recruit inflammatory cells, contributing to plaque instability by promoting neovascularization. Once plaque rupture occurs, monocyte EVs and endothelial EVs initiate the coagulation cascade by the expression of tissue factor contributing to thrombosis. EV = extracellular vesicles; miRNA = microRNA; NO = nitric oxide.