Endothelial cell-derived extracellular vesicles in atherosclerosis: the emerging value for diagnosis, risk stratification and prognostication

Abstract

Endothelial cell-derived extracellular vesicles are produced by both activated and apoptotic endothelial cells, and play a pivotal role in various physiological conditions such as inflammation, repair, programmed cell death, and immune responses. There is a large body of evidence on the dysregulation of synthesis and secretion of several types of endothelial cell-derived extracellular vesicles, which can then trigger microvascular inflammation, atherosclerotic plaque formation, plaque rupture, thrombosis and endothelial dysfunction. The development of atherosclerosis and cardiovascular events is associated with an increased number of apoptotic, endothelial cellderived vesicles and a decrease in activated, endothelial cell-derived vesicles. This review depicts the role of endothelial cell-derived extracellular vesicles in the manifestation and progression of atherosclerosis. We also discuss the clinical use and benefits of altering the immune phenotypes of extracellular vesicles originating from endothelial cells, to function as predictive biomarkers in both asymptomatic and subclinical atherosclerosis.

Extracellular Vesicles: Intercellular Communication Mediators in Antiphospholipid Syndrome

“…Extracellular vesicles are small particles composed of a phospholipid bilayer that encloses soluble cytosolic or endosomal material and nuclear components and, unlike a cell, are unable to replicate. EVs can be as small as the smallest physically possible unilamellar liposome (about 20-30 nm) or as large as 1 μm or more [14]. EVs serve as regulators of the transfer of biological information (proteins, nucleic acids, lipids and metabolites), which act both locally and remotely [15].…”

“…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.…”

“…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 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].…”

Effects of Chronic Kidney Disease and Uremic Toxins on Extracellular Vesicle Biology

“…Endothelial-cell-derived microvesicles can interact with many types of vascular cell and can induce pro-coagulative or pro-inflammatory responses [ 36 , 37 ]. Endothelial-cell-derived EVs carry a broad spectrum of biomolecules, such as miRs, which can induce various intracellular pathways involved in angiopoiesis, neovascularization, tissue regeneration, cytoprotection and wound healing [ 38 ].…”