{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T18:23:35Z","timestamp":1779906215887,"version":"3.53.1"},"reference-count":67,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,10]],"date-time":"2024-08-10T00:00:00Z","timestamp":1723248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NHLBI\/1F32HL167572-01A1 (DCH)","award":["23CDA1045594"],"award-info":[{"award-number":["23CDA1045594"]}]},{"name":"NIH\/NICHD\/K12HD047349(CS)","award":["23CDA1045594"],"award-info":[{"award-number":["23CDA1045594"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association CDA","doi-asserted-by":"publisher","award":["23CDA1045594"],"award-info":[{"award-number":["23CDA1045594"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH\/NHLBI\/1P01HL152961(CD)","award":["23CDA1045594"],"award-info":[{"award-number":["23CDA1045594"]}]},{"name":"NIH\/NHLBI\/1R35HL139726(EN)","award":["23CDA1045594"],"award-info":[{"award-number":["23CDA1045594"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Pulmonary hypertension (PH) is a progressive disease marked by pulmonary vascular remodeling and right ventricular failure. Inflammation and oxidative stress are critical in PH pathogenesis, with early pulmonary vascular inflammation preceding vascular remodeling. Extracellular superoxide dismutase (EC-SOD), a key vascular antioxidant enzyme, mitigates oxidative stress and protects against inflammation and fibrosis in diverse lung and vascular disease models. This study utilizes a murine hypobaric hypoxia model to investigate the role of lung EC-SOD on hypoxia-induced platelet activation and platelet lung accumulation, a critical factor in PH-related inflammation. We found that lung EC-SOD overexpression blocked hypoxia-induced platelet activation and platelet accumulation in the lung. Though lung EC-SOD overexpression increased lung EC-SOD content, it did not impact plasma extracellular SOD activity. However, ex vivo, exogenous extracellular SOD treatment specifically blunted convulxin-induced platelet activation but did not blunt platelet activation with thrombin or ADP. Our data identify platelets as a novel target of EC-SOD in response to hypoxia, providing a foundation to advance the understanding of dysregulated redox signaling and platelet activation in PH and other chronic hypoxic lung diseases.<\/jats:p>","DOI":"10.3390\/antiox13080975","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T05:23:27Z","timestamp":1723613007000},"page":"975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Lung EC-SOD Overexpression Prevents Hypoxia-Induced Platelet Activation and Lung Platelet Accumulation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2385-125X","authenticated-orcid":false,"given":"Daniel","family":"Colon Hidalgo","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Pulmonary and Critical Care, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Cardiovascular Pulmonary Research Group, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariah","family":"Jordan","sequence":"additional","affiliation":[{"name":"Cardiovascular Pulmonary Research Group, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Department of Pediatrics, Division of Neonatology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2846-9260","authenticated-orcid":false,"given":"Janelle N.","family":"Posey","sequence":"additional","affiliation":[{"name":"Cardiovascular Pulmonary Research Group, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Department of Pediatrics, Division of Neonatology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8707-260X","authenticated-orcid":false,"given":"Samuel D.","family":"Burciaga","sequence":"additional","affiliation":[{"name":"Cardiovascular Pulmonary Research Group, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6418-7172","authenticated-orcid":false,"given":"Thi-Tina N.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Cardiovascular Pulmonary Research Group, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Sul","sequence":"additional","affiliation":[{"name":"Cardiovascular Pulmonary Research Group, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Department of Pediatrics, Division of Critical Care, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6113-7815","authenticated-orcid":false,"given":"Caitlin V.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Cardiovascular Pulmonary Research Group, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Department of Pediatrics, Division of Critical Care, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassidy","family":"Delaney","sequence":"additional","affiliation":[{"name":"Cardiovascular Pulmonary Research Group, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Department of Pediatrics, Division of Neonatology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7229-5528","authenticated-orcid":false,"given":"Eva S.","family":"Nozik","sequence":"additional","affiliation":[{"name":"Cardiovascular Pulmonary Research Group, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Department of Pediatrics, Division of Critical Care, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.ccm.2013.08.010","article-title":"Epidemiology of pulmonary arterial 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