Extracellular vesicles as biomarkers and biovectors in primary aldosteronism

All cell types are capable of generating small heterogeneous vesicles called extracellular vesicles (EVs). EVs are released from activated or stressed parent cells into the extracellular space, such as plasma, cerebrovascular fluid, breast milk, urine, and saliva, and reflect the activation status and phenotype of the parent cell from which they were derived.1 Based on biogenesis, content, and size, EVs are classified as exosomes (40–100 nm), microparticles (also termed microvesicles; 100–1000 nm), and apoptotic bodies (1–5 µm).2 EVs were initially identified as cellular dust and considered to be cell debris. However, there is now good evidence in experimental and clinical studies demonstrating that EVs are biomarkers of disease, including cancer, metabolic disorders, and cardiovascular diseases.3,4 Moreover, it has become increasingly apparent that they are biologically active and are important signaling vehicles and regulators of local and distant cell-cell communication.1 EVs act as biovectors carrying cargo, such as proteins, lipids, receptors, RNA, microRNA, and enzymes, which are derived primarily from parent cells. They communicate with target cells, through diverse mechanisms, including release of cargo into the extracellular space, cell membrane binding, cell membrane fusion, and endocytosis by target cells. Through these interactions and transfer of cargo, EVs influence the function of other cells.2 For example, neutrophil-derived microvesicles carry cytokines, which function as proinflammatory mediators.1 Cancer cell–derived microparticles release metalloproteases and promote tumor invasion and metastases and platelet-derived microparticles transfer microRNA-142 into endothelial cells causing endothelial dysfunction.3,5