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      Antiplatelet Therapy for Acute Respiratory Distress Syndrome

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          Abstract

          Acute respiratory distress syndrome (ARDS) is a common and devastating syndrome that contributes to serious morbidities and mortality in critically ill patients. No known pharmacologic therapy is beneficial in the treatment of ARDS, and the only effective management is through a protective lung strategy. Platelets play a crucial role in the pathogenesis of ARDS, and antiplatelet therapy may be a potential medication for ARDS. In this review, we introduce the overall pathogenesis of ARDS, and then focus on platelet-related mechanisms underlying the development of ARDS, including platelet adhesion to the injured vessel wall, platelet-leukocyte-endothelium interactions, platelet-related lipid mediators, and neutrophil extracellular traps. We further summarize antiplatelet therapy, including aspirin, glycoprotein IIb/IIIa receptor antagonists, and P2Y12 inhibitors for ARDS in experimental and clinical studies and a meta-analysis. Novel aspirin-derived agents, aspirin-triggered lipoxin, and aspirin-triggered resolvin D1 are also described here. In this narrative review, we summarize the current knowledge of the role of platelets in the pathogenesis of ARDS, and the potential benefits of antiplatelet therapy for the prevention and treatment of ARDS.

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          Most cited references85

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          Netting neutrophils in autoimmune small-vessel vasculitis.

          Small-vessel vasculitis (SVV) is a chronic autoinflammatory condition linked to antineutrophil cytoplasm autoantibodies (ANCAs). Here we show that chromatin fibers, so-called neutrophil extracellular traps (NETs), are released by ANCA-stimulated neutrophils and contain the targeted autoantigens proteinase-3 (PR3) and myeloperoxidase (MPO). Deposition of NETs in inflamed kidneys and circulating MPO-DNA complexes suggest that NET formation triggers vasculitis and promotes the autoimmune response against neutrophil components in individuals with SVV.
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            Pathogenesis of Acute Respiratory Distress Syndrome

            Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure caused by noncardiogenic pulmonary edema. Despite five decades of basic and clinical research, there is still no effective pharmacotherapy for this condition and the treatment remains primarily supportive. It is critical to study the molecular and physiologic mechanisms that cause ARDS to improve our understanding of this syndrome and reduce mortality. The goal of this review is to describe our current understanding of the pathogenesis and pathophysiology of ARDS. First, we will describe how pulmonary edema fluid accumulates in ARDS due to lung inflammation and increased alveolar endothelial and epithelial permeabilities. Next, we will review how pulmonary edema fluid is normally cleared in the uninjured lung, and describe how these pathways are disrupted in ARDS. Finally, we will explain how clinical trials and preclinical studies of novel therapeutic agents have further refined our understanding of this condition, highlighting, in particular, the study of mesenchymal stromal cells in the treatment of ARDS.
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              Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation.

              Acute lung injury (ALI) causes high mortality, but its molecular mechanisms are poorly understood. Acid aspiration is a frequent cause of ALI, leading to neutrophil sequestration, increased permeability, and deterioration of gas exchange. We investigated the role of platelet-neutrophil interactions in a murine model of acid-induced ALI. Acid aspiration induced P-selectin-dependent platelet-neutrophil interactions in blood and in lung capillaries. Reducing circulating platelets or blocking P-selectin halted the development of ALI. Bone marrow chimeras showed that platelet, not endothelial, P-selectin was responsible for the injury. The interaction of platelets with neutrophils and endothelia was associated with TXA(2) formation, with detrimental effects on permeability and tissue function. Activated platelets induced endothelial expression of ICAM-1 and increased neutrophil adhesion. Inhibition of platelet-neutrophil aggregation improved gas exchange, reduced neutrophil recruitment and permeability, and prolonged survival. The key findings were confirmed in a sepsis-induced model of ALI. These findings may translate into improved clinical treatments for ALI.
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                Author and article information

                Journal
                Biomedicines
                Biomedicines
                biomedicines
                Biomedicines
                MDPI
                2227-9059
                21 July 2020
                July 2020
                : 8
                : 7
                : 230
                Affiliations
                [1 ]Department of Life Sciences, National Chung Hsing University, 145 Xingda Road, Taichung 402, Taiwan; chchen1@ 123456dragon.nchu.edu.tw
                [2 ]The iEGG and Animal Biotechnology Center, and the Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan
                [3 ]Division of Respiratory Therapy, Chia-Yi Christian Hospital, Chiayi 60002, Taiwan; 00614@ 123456cych.org.tw
                [4 ]Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei 110, Taiwan
                [5 ]Nutrition Research Center, Taipei Medical University Hospital, Taipei City 110, Taiwan
                [6 ]Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan
                [7 ]Division of Pulmonary and Critical Care Medicine, Chia-Yi Christian Hospital, Chiayi 60002, Taiwan
                Author notes
                [* ]Correspondence: f91625059@ 123456tmu.edu.tw (Y.-T.T.); peteralfa2004@ 123456gmail.com (W.C.); Tel.: +886-227361661 (Y.-T.T.); +886-5-2779365 (ext. 6172) (W.C.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-2461-9150
                https://orcid.org/0000-0002-4780-6496
                https://orcid.org/0000-0002-4152-4949
                Article
                biomedicines-08-00230
                10.3390/biomedicines8070230
                7399831
                32708068
                e348307f-a777-43a5-b2a0-291bf00cc642
                © 2020 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
                : 11 June 2020
                : 18 July 2020
                Categories
                Review

                acute respiratory distress syndrome,antiplatelet,aspirin,therapy

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