Abstract
Cells convey information among one another. One instrument employed to transmit data and constituents to specific (target) cells is extracellular vesicles (EVs). They originate from a variety of cells (endothelial, immune cells, platelets, mesenchymal stromal cells, etc.), and consequently, their surface characteristics and cargo vary according to the paternal cell. The cargo could be DNA, mRNA, microRNA, receptors, metabolites, cytoplasmic proteins, or pathological molecules, as a function of which EVs exert different effects upon endocytosis in recipient cells. Recently, EVs have become important participants in a variety of pathologies, including atherogenesis and coronavirus disease 2019 (COVID-19)-associated thrombosis. Herein, we summarize recent advances and some of our own results on the role of EVs in atherosclerotic cardiovascular diseases, and discuss their potential to function as signaling mediators, biomarkers and therapeutic agents. Since COVID-19 patients have a high rate of thrombotic events, a special section of the review is dedicated to the mechanism of thrombosis and the possible therapeutic potential of EVs in COVID-19-related thrombosis. Yet, EV mechanisms and their role in the transfer of information between cells in normal and pathological conditions remain to be explored.
Highlights
Over the course of evolution, the communities of cells of all organisms have found means to converse and communicate their physiological or pathological state with each other, reminding us of the well-known promise, “for better for worse, . . . in sickness and in health, . . . till death us do part”.Among the various methods of communication, the most recently discovered common instruments are extracellular vesicles (EVs), an assembly of cell-derived vesicles of different origins and sizes encompassing endosome-derived exosomes, plasma membrane-derived microvesicles and apoptotic bodies.EVs are released from activated or apoptotic cells carrying biological molecules such as DNA, mRNA, microRNA and others as cargo
[53] In addition, they carry proteins derived from the cytoplasm of the cells of origin: von Willebrand factor, monocyte chemoattractant protein-1 (MCP-1), matrix metallopeptidases (MMP2, MMP9), vascular endothelial growth factor (VEGF), DNA, mRNAs, miRNAs, noncoding RNAs and peroxisome proliferator-activated receptor gamma [46,54–58] (Figure 1)
The atherogenic process can be arbitrarily divided into six main stages: (1) endothelial cell (EC) activation on account of the accumulation of plasma oxidativelymodified, low-density lipoproteins (MLp) that induce changes in EC constitutive function; (2) EC dysfunction manifested by the expression of novel cell adhesion molecules; (3) robust inflammation, i.e., recruitment of the circulating immune cells; (4) migration of smooth muscle cells (SMCs) from the media to intima, forming the fibrous plaque; (5) the development of the calcified fibro-lipid plaque made of apoptotic resident and immune cells, and calcium deposition that leads to (6) the unstable fibro-lipid plaque, and the ensuing rupture, exposure of the vascular extracellular matrix, platelet adherence and the formation of thrombus [12,62–65] (Figure 2)
Summary
Over the course of evolution, the communities of cells of all organisms have found means to converse and communicate their physiological or pathological state with each other, reminding us of the well-known promise, “for better for worse, . . . in sickness and in health, . . . till death us do part” (marriage vows in the Catholic church). This review will focus on the role of EVs in atherosclerosis and thrombosis, the major causes of death in developed countries and major public health problems. Recent studies have been focused on the identification of new compounds that could be used either as biomarkers or targets for new therapies to stop the evolution of atherosclerotic plaques In this regard, the discovery of the presence and determining the role of EVs in all stages of plaque formation was key. We present here the pathophysiology of atherosclerosis, focusing on the cells and molecules involved, immune cell activation and inflammatory processes, the implication of EVs in the atheroma progression, and highlight promising new directions involving EVs as biomarkers and therapeutic agents. We will discuss novel data regarding the role of EVs in COVID-19-generated thrombotic events and the potential of EV-based therapies as a new/additional remedy for this disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
