Year: 2024
Type: article
Study design: Observational Study
Abstract: 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. 42, 361–377.
Source: Antioxidants and Redox Signaling
Authors: Samar Farha, Kewal Asosingh, Paul M. Hassoun, John Barnard, Suzy Comhair, Andrew Reichard, Nicholas Wanner, Milena Radeva, Micheala A. Aldred, Gerald J. Beck, Erika Berman-Rosenzweig, Barry A. Borlaug, J. Emanuel Finet, Robert P. Frantz, Gabriele Grunig, Anna R. Hemnes, Nicholas Hill, Evelyn M. Horn, Christine Jellis, Jane A. Leopold, Reena Mehra, Margaret M. Park, Franz P. Rischard, W.H. Wilson Tang, Serpil C. Erzurum, the PVDOMICS Study Group
Institutions: Cleveland Clinic, Johns Hopkins University, Johns Hopkins Hospital, Indiana University Indianapolis, Indiana University School of Medicine, Columbia University, Mayo Clinic, New York University, Vanderbilt University Medical Center, Tufts Medical Center, Weill Cornell Medicine, Weill Cornell Medical Center, Brigham and Women's Hospital, Harvard University, University of Washington, University of Arizona
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4405208140