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      Biology and Role of Extracellular Vesicles (EVs) in the Pathogenesis of Thrombosis

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          Abstract

          Extracellular vesicles (EVs) are well-established mediators of cell-to-cell communication. EVs can be released by every cell type and they can be classified into three major groups according to their biogenesis, dimension, density, and predominant protein markers: exosomes, microvesicles, and apoptotic bodies. During their formation, EVs associate with specific cargo from their parental cell that can include RNAs, free fatty acids, surface receptors, and proteins. The biological function of EVs is to maintain cellular and tissue homeostasis by transferring critical biological cargos to distal or neighboring recipient cells. On the other hand, their role in intercellular communication may also contribute to the pathogenesis of several diseases, including thrombosis. More recently, their physiological and biochemical properties have suggested their use as a therapeutic tool in tissue regeneration as well as a novel option for drug delivery. In this review, we will summarize the impact of EVs released from blood and vascular cells in arterial and venous thrombosis, describing the mechanisms by which EVs affect thrombosis and their potential clinical applications.

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          Most cited references181

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          Biogenesis and secretion of exosomes.

          Although observed for several decades, the release of membrane-enclosed vesicles by cells into their surrounding environment has been the subject of increasing interest in the past few years, which led to the creation, in 2012, of a scientific society dedicated to the subject: the International Society for Extracellular Vesicles. Convincing evidence that vesicles allow exchange of complex information fuelled this rise in interest. But it has also become clear that different types of secreted vesicles co-exist, with different intracellular origins and modes of formation, and thus probably different compositions and functions. Exosomes are one sub-type of secreted vesicles. They form inside eukaryotic cells in multivesicular compartments, and are secreted when these compartments fuse with the plasma membrane. Interestingly, different families of molecules have been shown to allow intracellular formation of exosomes and their subsequent secretion, which suggests that even among exosomes different sub-types exist. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Epidemiology of venous thromboembolism.

            John Heit (2015)
            Thrombosis can affect any venous circulation. Venous thromboembolism (VTE) includes deep-vein thrombosis of the leg or pelvis, and its complication, pulmonary embolism. VTE is a fairly common disease, particularly in older age, and is associated with reduced survival, substantial health-care costs, and a high rate of recurrence. VTE is a complex (multifactorial) disease, involving interactions between acquired or inherited predispositions to thrombosis and various risk factors. Major risk factors for incident VTE include hospitalization for surgery or acute illness, active cancer, neurological disease with leg paresis, nursing-home confinement, trauma or fracture, superficial vein thrombosis, and-in women-pregnancy and puerperium, oral contraception, and hormone therapy. Although independent risk factors for incident VTE and predictors of VTE recurrence have been identified, and effective primary and secondary prophylaxis is available, the occurrence of VTE seems to be fairly constant, or even increasing.
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              Microparticles in hemostasis and thrombosis.

              Blood contains microparticles (MPs) derived from a variety of cell types, including platelets, monocytes, and endothelial cells. In addition, tumors release MPs into the circulation. MPs are formed from membrane blebs that are released from the cell surface by proteolytic cleavage of the cytoskeleton. All MPs are procoagulant because they provide a membrane surface for the assembly of components of the coagulation protease cascade. Importantly, procoagulant activity is increased by the presence of anionic phospholipids, particularly phosphatidylserine (PS), and the procoagulant protein tissue factor (TF), which is the major cellular activator of the clotting cascade. High levels of platelet-derived PS(+) MPs are present in healthy individuals, whereas the number of TF(+), PS(+) MPs is undetectable or very low. However, levels of PS(+), TF(+) MPs are readily detected in a variety of diseases, and monocytes appear to be the primary cellular source. In cancer, PS(+), TF(+) MPs are derived from tumors and may serve as a useful biomarker to identify patients at risk for venous thrombosis. This review will summarize our current knowledge of the role of procoagulant MPs in hemostasis and thrombosis.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                11 June 2019
                June 2019
                : 20
                : 11
                : 2840
                Affiliations
                [1 ]Unit of Heart-Brain Axis: Cellular and Molecular Mechanisms, Centro Cardiologico Monzino IRCCS, 20138 Milano, Italy; marta.zara@ 123456ccfm.it (M.Z.); patrizia.amadio@ 123456ccfm.it (P.A.)
                [2 ]Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy; gianni.guidetti@ 123456unipv.it (G.F.G.); ilaria.canobbio@ 123456unipv.it (I.C.); mtorti@ 123456unipv.it (M.T.)
                [3 ]Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milano, Italy; marina.camera@ 123456unimi.it
                [4 ]Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino IRCCS, 20138 Milano, Italy
                [5 ]Scientific Direction, Centro Cardiologico Monzino IRCCS, 20138 Milano, Italy; elena.tremoli@ 123456ccfm.it
                Author notes
                [* ]Correspondence: silvia.barbieri@ 123456ccfm.it ; Tel.: +39-02-58002021
                Author information
                https://orcid.org/0000-0002-7486-2637
                Article
                ijms-20-02840
                10.3390/ijms20112840
                6600675
                31212641
                d3c0dfac-f848-4940-8211-1234588187c2
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 May 2019
                : 07 June 2019
                Categories
                Review

                Molecular biology
                extracellular vesicles,microvesicles,exosomes,biomarker,arterial thrombosis,venous thrombosis

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