**3. Extracellular vesicles in vascular pathologies**

The main cell types involved in vascular hemostasis are endothelial cells, platelets and monocytes. All these cells release EVs, which leads to a complex interplay between different vesicles and different cells. EVs are continuously released in low concentrations from the cells into the intercellular environment, but this is greatly increased during cellular activation and apoptosis. EVs transmit various biological information (in the form of proteins, lipids and nucleic acids). Travelling through the bloodstream, EVs serve as local or distant messengers that transmit information to a variety of cells and tissues. Hemostasis is a very strictly regulated process that maintains normal function of vasculature despite the presence of triggers, such as injury and/or infection. One of the consequences of an altered hemostatic balance is the formation of thrombi, a process in which EVs play an important role [15]. EVs coming from activated cells have been shown to have both procoagulant and proinflammatory effects. Procoagulant effects are related to the fact that some EVs contain anionic phospholipids, mainly phosphatidylserine (PS), on their surface, which contributes to the assembly and activation of the prothrombinase complexes, thus promoting thrombin formation [34]. However, not all EVs carry PS on their surface, suggesting the involvement of other mechanisms contributing to the procoagulant state [35], including other important coagulation factors, such as tissue factor (TF), Factor XII [36], and reduced activity of tissue factor pathway inhibitor (TFPI) and thrombomodulin on endothelial cells [37]. In addition, EVs also induce the expression of adhesion molecules; integrins and selectins on the recipient cells causing platelets, monocytes, and endothelial cells to interact more intensively with each another. Finally, EVs also contribute significantly to the proinflammatory state in the vascular microenvironment by delivering or inducing certain cytokines and chemokines and by transferring nucleic acids and lipids [38]. The effects that these EVs have on different cell types disrupt the normal functioning of the vascular system, leading to the development of different pathologies, including deep vein thrombosis or pulmonary embolism [7] and cardiovascular diseases (atherosclerosis [39], hypertension [8], myocardial infarction [40] and stroke [41]).
