Endothelial Extracellular Vesicles-Promises and Challenges

Abstract

Extracellular vesicles, including exosomes, microparticles, and apoptotic bodies, are phospholipid bilayer-enclosed vesicles that have once been considered as cell debris lacking biological functions. However, they have recently gained immense interest in the scientific community due to their role in intercellular communication, immunity, tissue regeneration as well as in the onset, and progression of various pathologic conditions. Extracellular vesicles of endothelial origin have been found to play a versatile role in the human body, since they are on the one hand known to contribute to cardiovascular diseases, but on the other hand have also been reported to promote endothelial cell survival. Hence, endothelial extracellular vesicles hold promising therapeutic potential to be used as a new tool to detect as well as treat a great number of diseases. This calls for clinically approved, standardized, and efficient isolation and characterization protocols to harvest and purify endothelial extracellular vesicles. However, such methods and techniques to fulfill stringent requirements for clinical trials have yet to be developed or are not harmonized internationally. In this review, recent advances and challenges in the field of endothelial extracellular vesicle research are discussed and current problems and limitations regarding isolation and characterization are pointed out.

Keywords: endothelial cells; exosomes; extracellular vesicles; microparticles; pathology.

Figure 1

Summary of triggers that mediate the release of microparticles (MPs) from endothelial cells (ECs). Release of endothelial microparticles (EMPs) into the circulation is induced in response to pro-inflammatory cytokines, e.g., TNF-α, IL-1, IFN-γ, and LPS, as well as thrombin, CRP and PAI-1. While high shear stress inhibits the release of EMPs, results on the effect of hypoxia on EMP release remain controversial. Several markers have been reported to be used alone or in combination to detect EMPs, e.g., AnnexinV, CD31, CD106, CD144, and CD62E. TNF-α, tumor necrosis factor α; IL-1, interleukin-1; IFN-γ, interferon-γ; LPS, lipopolysaccharide; CRP, C-reactive protein; PAI-1, plasminogen activator inhibitor-1.