Abstract

Extracellular vesicles (EVs) compose a heterogenous group of membrane-derived particles, including exosomes, microvesicles and apoptotic bodies, which are released into the extracellular environment in response to proinflammatory or proapoptotic stimuli. From earlier studies suggesting that EV shedding constitutes a cellular clearance mechanism, it has become evident that EV formation, secretion and uptake represent important mechanisms of intercellular communication and exchange of a wide variety of molecules, with relevance in both physiological and pathological situations. The putative role of EVs in hemostasis and thrombosis is supported by clinical and experimental studies unraveling how these cell-derived structures affect clot formation (and resolution). From those studies, it has become clear that the prothrombotic effects of EVs are not restricted to the exposure of tissue factor (TF) and phosphatidylserines (PS), but also involve multiplication of procoagulant surfaces, cross-linking of different cellular players at the site of injury and transfer of activation signals to other cell types. Here, we summarize the existing and novel clinical and experimental evidence on the role and function of EVs during arterial and venous thrombus formation and how they may be used as biomarkers as well as therapeutic vectors.

Highlights

  • Elevated numbers of monocyte-derived tissue factor (TF)-positive MPs and a higher procoagulant activity of platelet-free plasma were detected in patients with initial or recurrent deep vein thrombosis (DVT) compared to sex- and age-matched healthy controls [195]

  • That the increased risk of thrombosis, in the venous system, associated with some forms of cancer is linked to TF-positive MPs was confirmed in another experimental study by showing larger clots following inferior Vena cava (IVC) ligation in mice bearing human pancreatic tumors compared to controls [239]

  • Extracellular vesicles (EVs)-triggered venous thrombosis was reduced in mice lacking PAR4 or treated with clopidogrel supporting a role for TF-induced platelet activation in this model

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. EVs have been identified as mediators of cell-to-cell communication due to their ability to contain and transfer bioactive molecular cargo, such as transmembrane and cytosolic proteins, coding and non-coding RNA, or DNA, to both distant and neighboring cells. Their capacity of exchanging components between cells and their presence in the majority of body fluids suggests that they participate in normal homeostatic processes as well as pathological disease states, and that they may serve as biomarkers and therapeutic vehicles. We summarize the existing and novel clinical and experimental evidence on the role and function of EVs during arterial and venous thrombus formation and how they may be used as biomarkers as well as therapeutic vectors

Extracellular Vesicles
General
Activation and Inflammation
Age and Senescence
Cell Death and Apoptosis
Fate and Effects of EVs on Recipient Cells
Extracellular Vesicles and Thrombosis
EVs and Thrombosis in the Arterial System
Findings in Human Studies
Extracellular Vesicles and Thrombosis Associated with COVID-19 Infection
Findings in Mouse Models
Main Findings
10. Conclusions
Full Text
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