Endothelial Extracellular Vesicles: From Keepers of Health to Messengers of Disease

Abstract

Endothelium has a rich vesicular network that allows the exchange of macromolecules between blood and parenchymal cells. This feature of endothelial cells, along with their polarized secretory machinery, makes them the second major contributor, after platelets, to the particulate secretome in circulation. Extracellular vesicles (EVs) produced by the endothelial cells mirror the remarkable molecular heterogeneity of their parent cells. Cargo molecules carried by EVs were shown to contribute to the physiological functions of endothelium and may support the plasticity and adaptation of endothelial cells in a paracrine manner. Endothelium-derived vesicles can also contribute to the pathogenesis of cardiovascular disease or can serve as prognostic or diagnostic biomarkers. Finally, endothelium-derived EVs can be used as therapeutic tools to target endothelium for drug delivery or target stromal cells via the endothelial cells. In this review we revisit the recent evidence on the heterogeneity and plasticity of endothelial cells and their EVs. We discuss the role of endothelial EVs in the maintenance of vascular homeostasis along with their contributions to endothelial adaptation and dysfunction. Finally, we evaluate the potential of endothelial EVs as disease biomarkers and their leverage as therapeutic tools.

Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells

“…Exosomes are small vesicles with a diameter of 30-150 nm naturally secreted by cells [ 33 ], and they can be used as potential carriers to deliver drugs, therapeutic genes or proteins in clinical treatment due to their stability and high biocompatibility [ 34 – 37 ]. In current study, the exosomes produced from mouse aortic endothelial cells were selected as vehicles of gene therapy as it mirror the marker molecules of parent cells and was associated with many physiological progresses such as anti-inflammation, anti-oxidation and the inhibition of endothelial-to-mesenchymal transition (EndMT) [ 12 , 22 ]. However, normal exosomes cannot target specific cells.…”

“…Exosomes produced by the endothelial cells share the similar marker molecules with progenitor cells and contribute to the physiological functions of endothelium as well as the pathogenesis of cardiovascular disease. Thus we selected exosomes derived from mouse aortic endothelial cells as the vehicles of gene therapy [ 12 , 22 ].…”

New insights into the pathogenesis of cardiac papillary fibroelastomas

“…It is well established that EVs are key players in cell-to-cell communication both under physiological and pathological conditions [24][25][26][27]. Extracellular vesicles are capable of transferring biological information because they contain a diverse cargo of lipids, proteins, mRNAs, miRNAs, DNA fragments, and metabolites, which can modulate biological functions in target cells [28,29]. Under physiological conditions, endothelial cells secrete EVs into the blood in low concentrations.…”

“…However, EVs levels have been shown to increase in cardiovascular diseases involving endothelial injury or dysfunction [30][31][32][33]. Currently, little is known about the physiological role of EVs derived from EC, however, the latest reviews suggest that EVs may be involved in the maintenance of endothelial homeostasis [29,34] and fetal development [29]. As mentioned above, EVs have been implicated in the induction of EndoMT in various pathological conditions, for example: melanoma-derived EVs induced EndoMT in Human umbilical vein endothelial cells (HUVECs) in vitro [35], adipose microvascular endothelial cells undergo in vitro EndoMT when exposed to EVs obtained from adipose tissue of patients with obesity [29].…”

Molecular Research in Cardiovascular Disease

“…Keeping within the same line of research, endothelial EV have a role in endothelial physiology, as exposed by Mathiesen et al [10]. Injured endothelial cells can be repaired and regenerated by complement-induced apoptosis by shedding EV rich in caspase-3, protecting the endothelium against stress, as Abid Hussein et al showed [11].…”