{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T01:47:13Z","timestamp":1789264033620,"version":"build-2803163510"},"reference-count":73,"publisher":"SAGE Publications","issue":"7-9","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>Alterations of mitochondrial bioenergetics and arginine metabolism are universally present and mechanistically linked to pulmonary arterial hypertension (PAH), but there is little knowledge of arginine metabolism and mitochondrial functions across the different pulmonary hypertension (PH) groups. We hypothesize that abnormalities in mitochondrial functions are present across all PH groups and associated with clinical phenotypes. We test the hypothesis in PH patients and healthy controls from the Pulmonary Vascular Disease Phenomics Program cohort, who had comprehensive clinical phenotyping and follow-up for at least 4 years for death or transplant status. Mitochondrial transmembrane potential, superoxide production, and mass were measured by flow cytometry in fresh platelets. Metabolomics analysis was performed on plasma samples. Global arginine bioavailability was calculated as the ratio of arginine\/(ornithine+citrulline).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Global arginine bioavailability is consistently lower than controls in all PH groups. Although the mitochondrial mass is similar across all PH groups and controls, superoxide production and transmembrane potential vary across groups. Mitochondrial superoxide is higher in group 1 PAH and lowest in group 3 compared with other groups, while transmembrane potential is lower in group 1 PAH than controls or group 3. The alterations in mitochondrial functions of group 1 PAH are associated with changes in fatty acid metabolism. Mitochondrial transmembrane potential in group 1 PAH is associated with transplant-free survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      While alterations in mitochondrial function are found in all PH groups, group 1 PAH has a unique mitochondrial phenotype with greater superoxide and lower transmembrane potential linked to fatty acid metabolism, and clinically to survival.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      42, 361\u2013377.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2024.0557","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T05:24:46Z","timestamp":1733808286000},"page":"361-377","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Alterations in Mitochondrial Function in Pulmonary Vascular Diseases"],"prefix":"10.1177","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4800-8928","authenticated-orcid":false,"given":"Samar","family":"Farha","sequence":"first","affiliation":[{"name":"Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA."},{"name":"Lerner Research Institute, Cleveland Clinic, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewal","family":"Asosingh","sequence":"additional","affiliation":[{"name":"Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Hassoun","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Barnard","sequence":"additional","affiliation":[{"name":"Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzy","family":"Comhair","sequence":"additional","affiliation":[{"name":"Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Reichard","sequence":"additional","affiliation":[{"name":"Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Wanner","sequence":"additional","affiliation":[{"name":"Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Radeva","sequence":"additional","affiliation":[{"name":"Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micheala A.","family":"Aldred","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine Indianapolis, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald J.","family":"Beck","sequence":"additional","affiliation":[{"name":"Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Berman-Rosenzweig","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Medicine, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry A.","family":"Borlaug","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Emanuel","family":"Finet","sequence":"additional","affiliation":[{"name":"Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Frantz","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Grunig","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine, New York University Grossman School of Medicine, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna R.","family":"Hemnes","sequence":"additional","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Hill","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, Tufts Medical Center, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn M.","family":"Horn","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Weill Cornell Medical Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Jellis","sequence":"additional","affiliation":[{"name":"Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane A.","family":"Leopold","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Mehra","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret M.","family":"Park","sequence":"additional","affiliation":[{"name":"Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz P.","family":"Rischard","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, Arizona, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.H. 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