**2.2 Biological role of EVs**

The key biological function of EVs is cell to cell communication and the transfer of biological materials that act closely, but also, and more importantly, remotely. Cargo within the EVs is protected from degradation in the bloodstream and can be successfully transferred to specific cells of interest, affecting several biological functions of these cells. EVs can transfer a wide variety of molecules: heat shock proteins (HSP-90, HSP-70), interleukins (IL), such as tumor necrosis factor-alpha (TNFα), acute phase proteins, such as serum amyloid A [20], enzymes, peptides, growth factors [14]. Therefore, EVs have a wide range of biological functions including immune response, antigen presentation, and the transfer of RNA, including micro RNA (miR) and DNA. Given the fact that EVs migrate through the bloodstream they can have pleiotropic effects that are likely to affect every tissue in the body [14]. In immunity, they modulate immune cells, cell–cell interactions, and transfer of cytokines and chemokines. In the heart and vessels, they stimulate

#### **Figure 1.**

*Classification of EVs. EVs can be classified according to their size (Small <100 nm or < 200 nm, Medium/ large >200 nm), density (Low, Medium, High) with a defined density range, biogenesis pathway (Exosomes; endosomal derived, Microvesicles; membrane derived and Apoptotic bodies; released upon cell apoptosis) or biochemical composition defining EVs origin, surface proteins or cargo. Created with BioRender.com.*

coagulation and thrombosis, modulate angiogenesis, calcification and vascular repair. In the adipose tissue, they modulate angiogenesis, inflammation, cell differentiation and secretion of cytokines. In the bone marrow, they are involved in cell–cell cooperation, cell proliferation, differentiation and maturation. In the central nervous system, they are involved in the integration of neurons and various glial cells, modulate angiogenesis, neuronal plasticity and myelination. In the blood, they influence activation and aggregation of platelets, are directly involved in coagulation, as well as cargo transfer of procoagulant or anticoagulant molecules, cytokines and growth factors [14].
