Fig. 3.

EV signalling in vascular inflammation and atherosclerosis. Brief schematic representation of EVs and their roles in the steps of atherosclerotic lesion progression. (A) During fatty streak formation, EC-derived EVs promote endothelial ICAM-1, VCAM-1 expression, reduction of NO production, oxLDL uptake by macrophages and macrophage migration. Monocyte-derived EVs induce vascular inflammation (expression of IL-6, IL-1β), upregulation of adhesion molecules in ECs (ICAM-1, VCAM-1 and E-selectin) and vascular cell death. Foam cell-EVs and platelet-EVs can induce SMC proliferation and migration, aggravating the progression of the disease. Crosstalk between cells is fundamental; SMC-EVs can promote EC migration and via miRNA transfer promote tight junction destruction. (B) Dead cells accumulate in the plaque's necrotic core. Platelet, endothelial, dendritic and monocytic-derived EVs encapsulate cell death related proteases: caspase-1 and caspase-3 that can induce macrophage apoptosis. Monocyte-EVs can promote SMC death via caspase-1 and participate in formation of the atherosclerotic plaque. (C) Weakening of the fibrous cap is the main cause of plaque rupture. EVs from various sources (macrophage, neutrophil, endothelial) encapsulate MMPs and may degrade extracellular matrix and destabilize the plaque. Platelet and monocyte derived EVs can also enhance thrombus formation.