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      Endothelial- and Immune Cell-Derived Extracellular Vesicles in the Regulation of Cardiovascular Health and Disease

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          Summary

          Intercellular signaling by extracellular vesicles (EVs) is a route of cell-cell crosstalk that allows cells to deliver biological messages to specific recipient cells. EVs convey these messages through their distinct cargoes consisting of cytokines, proteins, nucleic acids, and lipids, which they transport from the donor cell to the recipient cell. In cardiovascular disease (CVD), endothelial- and immune cell-derived EVs are emerging as key players in different stages of disease development. EVs can contribute to atherosclerosis development and progression by promoting endothelial dysfunction, intravascular calcification, unstable plaque progression, and thrombus formation after rupture. In contrast, an increasing body of evidence highlights the beneficial effects of certain EVs on vascular function and endothelial regeneration. However, the effects of EVs in CVD are extremely complex and depend on the cellular origin, the functional state of the releasing cells, the biological content, and the diverse recipient cells. This paper summarizes recent progress in our understanding of EV signaling in cardiovascular health and disease and its emerging potential as a therapeutic agent.

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          Most cited references75

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          Inflammation in atherosclerosis: from pathophysiology to practice.

          Until recently, most envisaged atherosclerosis as a bland arterial collection of cholesterol, complicated by smooth muscle cell accumulation. According to that concept, endothelial denuding injury led to platelet aggregation and release of platelet factors which would trigger the proliferation of smooth muscle cells in the arterial intima. These cells would then elaborate an extracellular matrix that would entrap lipoproteins, forming the nidus of the atherosclerotic plaque. Beyond the vascular smooth muscle cells long recognized in atherosclerotic lesions, subsequent investigations identified immune cells and mediators at work in atheromata, implicating inflammation in this disease. Multiple independent pathways of evidence now pinpoint inflammation as a key regulatory process that links multiple risk factors for atherosclerosis and its complications with altered arterial biology. Knowledge has burgeoned regarding the operation of both innate and adaptive arms of immunity in atherogenesis, their interplay, and the balance of stimulatory and inhibitory pathways that regulate their participation in atheroma formation and complication. This revolution in our thinking about the pathophysiology of atherosclerosis has now begun to provide clinical insight and practical tools that may aid patient management. This review provides an update of the role of inflammation in atherogenesis and highlights how translation of these advances in basic science promises to change clinical practice.
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            Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication.

            Normal and malignant cells shed from their surface membranes as well as secrete from the endosomal membrane compartment circular membrane fragments called microvesicles (MV). MV that are released from viable cells are usually smaller in size compared to the apoptotic bodies derived from damaged cells and unlike them do not contain fragmented DNA. Growing experimental evidence indicates that MV are an underappreciated component of the cell environment and play an important pleiotropic role in many biological processes. Generally, MV are enriched in various bioactive molecules and may (i) directly stimulate cells as a kind of 'signaling complex', (ii) transfer membrane receptors, proteins, mRNA and organelles (e.g., mitochondria) between cells and finally (iii) deliver infectious agents into cells (e.g., human immuno deficiency virus, prions). In this review, we discuss the pleiotropic effects of MV that are important for communication between cells, as well as the role of MV in carcinogenesis, coagulation, immune responses and modulation of susceptibility/infectability of cells to retroviruses or prions.
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              The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins.

              Selective trafficking of membrane proteins to lysosomes for destruction is required for proper cell signalling and metabolism. Ubiquitylation aids this process by specifying which proteins should be transported to the lysosome lumen by the multivesicular endosome pathway. The endosomal sorting complex required for transport (ESCRT) machinery sorts cargo labelled with ubiquitin into invaginations of endosome membranes. Then, through a highly conserved mechanism also used in cytokinesis and viral budding, it mediates the breaking off of the cargo-containing intraluminal vesicles from the perimeter membrane. The involvement of the ESCRT machinery in suppressing diseases such as cancer, neurodegeneration and infections underscores its importance to the cell.
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                Author and article information

                Contributors
                Journal
                JACC Basic Transl Sci
                JACC Basic Transl Sci
                JACC: Basic to Translational Science
                Elsevier
                2452-302X
                25 December 2017
                December 2017
                25 December 2017
                : 2
                : 6
                : 790-807
                Affiliations
                [a ]Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany
                [b ]Department of Cardiology, Second Hospital of Jilin University, Nanguan District, Changchun, China
                [c ]Institute of Pharmacology and Toxicology, University of Bonn, Bonn, Germany
                Author notes
                [] Address for correspondence: Dr. Felix Jansen, Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany. felix.jansen@ 123456ukbonn.de
                [∗∗ ]Dr. Nikos Werner, Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany. nwerner@ 123456uni-bonn.de
                [∗∗∗ ]Dr. Qian Li, Department of Cardiology, Second Hospital of Jilin University, 218 Ziqiang Street, Nanguan District, Changchun 130000, China.
                Article
                S2452-302X(17)30230-9
                10.1016/j.jacbts.2017.08.004
                6059011
                30062186
                7eb4cf82-90cf-4be4-818c-35082c7acddc
                © 2017 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 7 July 2017
                : 14 August 2017
                : 14 August 2017
                Categories
                STATE-OF-THE-ART REVIEW

                cardiovascular disease,extracellular vesicles,microvesicles,cvd, cardiovascular disease,ec, endothelial cell,emv, endothelial cell-derived microvesicles,escrt, endosomal sorting complex required for transport,il, interleukin,mirna, microrna,mv, microvesicles,no, nitric oxide,peg, polyethylene glycol,tgf, transforming growth factor

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