Alterations in Mitochondrial Function in Pulmonary Vascular Diseases.

Autor: Farha S; Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Lerner Research Institute, Cleveland Clinic, Ohio, USA., Asosingh K; Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA., Hassoun PM; Division of Pulmonary and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland, USA., Barnard J; Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA., Comhair S; Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA., Reichard A; Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA., Wanner N; Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA., Radeva M; Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA., Aldred MA; Department of Medicine, Indiana University School of Medicine Indianapolis, Indianapolis, Indiana, USA., Beck GJ; Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA., Berman-Rosenzweig E; Department of Pediatrics and Medicine, Columbia University, New York, New York, USA., Borlaug BA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA., Finet JE; Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA., Frantz RP; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA., Grunig G; Department of Environmental Medicine, New York University Grossman School of Medicine, New York, New York, USA., Hemnes AR; Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Hill N; Division of Pulmonary, Critical Care, and Sleep Medicine, Tufts Medical Center, Boston, Massachusetts, USA., Horn EM; Division of Cardiology, Weill Cornell Medical Center, New York, New York, USA., Jellis C; Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA., Leopold JA; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Mehra R; Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, Washington, USA., Park MM; Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA., Rischard FP; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, Arizona, USA., Tang WHW; Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA., Erzurum SC; Integrated Hospital-Care Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Lerner Research Institute, Cleveland Clinic, Ohio, USA.
Jazyk: angličtina
Zdroj: Antioxidants & redox signaling [Antioxid Redox Signal] 2024 Dec 10. Date of Electronic Publication: 2024 Dec 10.
DOI: 10.1089/ars.2024.0557
Abstrakt: Aims: 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). Results: 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. Conclusion: 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. Antioxid. Redox Signal. 00, 000-000.
Databáze: MEDLINE