Dysregulated Tricarboxylic Acid Cycle Metabolism Is Associated With Right Ventricular Maladaptation in Pulmonary Vascular Disease
We identify an association between circulating TCA cycle intermediate levels and RV-PA uncoupling in 2 independent cohorts, and dysregulated TCA cycle metabolism in decompensated PA hypertension RVs, suggesting that aberrant TCA cycle metabolism could represent a hallmark of RV maladaptation in PA hypertension. Further study of this pathway is warranted to develop novel biomarkers of RV function or RV-targeted therapies.
Authors
- Jason K. Lempel (ORCID: https://orcid.org/0000-0001-6772-5274)
- Rachel L. Damico (ORCID: https://orcid.org/0000-0002-2584-1557)
- Stefan Sherer
- Blessing Enobun (ORCID: https://orcid.org/0000-0003-1819-0562)
- Simon P. Wells (ORCID: https://orcid.org/0000-0002-8071-2563)
- Jill Odabashian
- Aisling M. Flinn (ORCID: https://orcid.org/0000-0001-9397-0214)
- Alexandra Kanta
- Karthik Suresh (ORCID: https://orcid.org/0000-0003-2920-0949)
- Micheala A. Aldred (ORCID: https://orcid.org/0000-0002-7390-9181)
- Ivan M. Robbins (ORCID: https://orcid.org/0000-0003-0883-3675)
- Joan Aylor
- Garvan C. Kane (ORCID: https://orcid.org/0000-0002-4308-6356)
- Evan L. Brittain (ORCID: https://orcid.org/0000-0001-5843-3392)
- James M. Cunningham (ORCID: https://orcid.org/0000-0003-0541-4862)
- Marc K. Halushka (ORCID: https://orcid.org/0000-0002-7112-7389)
- José Ramos (ORCID: https://orcid.org/0009-0007-5362-1141)
- Miriam Jacob (ORCID: https://orcid.org/0000-0002-2529-7467)
- M Geraci
- J. Emanuel Finet (ORCID: https://orcid.org/0000-0002-0156-6757)
- Belinda Willard (ORCID: https://orcid.org/0000-0001-6884-6369)
- Udhay Krishnan (ORCID: https://orcid.org/0000-0002-5150-1089)
- Michael P. Gray (ORCID: https://orcid.org/0000-0003-1154-3011)
- Michael J. Krowka (ORCID: https://orcid.org/0000-0003-4599-4953)
- Paul M. Hassoun (ORCID: https://orcid.org/0000-0003-0601-4975)
- Lene Hansen (ORCID: https://orcid.org/0000-0001-7918-3943)
- Gyu Tae Park (ORCID: https://orcid.org/0000-0002-6649-8783)
- Wendy K. Chung (ORCID: https://orcid.org/0000-0003-3438-5685)
- Clara Collart
- A. Balasubramanian (ORCID: https://orcid.org/0000-0001-6896-5069)
- Atta Behfar (ORCID: https://orcid.org/0000-0003-3775-5784)
- Feixiong Cheng (ORCID: https://orcid.org/0000-0002-1736-2847)
- Aaron B. Waxman (ORCID: https://orcid.org/0000-0001-7797-0361)
- B Beck
- Brett Larive
- Gerald J. Beck (ORCID: https://orcid.org/0000-0002-9514-591X)
- Barry Schmetter
- SERPIL CEM ERZURUM (ORCID: https://orcid.org/0000-0001-5202-9065)
- Denise Head (ORCID: https://orcid.org/0000-0002-7069-2634)
- James C. Fang (ORCID: https://orcid.org/0000-0003-2427-9504)
- John Barnard (ORCID: https://orcid.org/0000-0003-2403-8268)
- Margaret M. Redfield (ORCID: https://orcid.org/0000-0002-0946-7518)
- Eric E. Williamson (ORCID: https://orcid.org/0000-0002-2066-9612)
- Barry A. Borlaug (ORCID: https://orcid.org/0000-0001-9375-0596)
- Deborah Kwon (ORCID: https://orcid.org/0000-0003-2191-4111)
- Jacqueline Sharp
- Brenda Wong (ORCID: https://orcid.org/0000-0002-0971-9789)
- Stephen C. Mathai (ORCID: https://orcid.org/0000-0003-3188-7209)
- Julia Lohman
- Jason X.‐J. Yuan (ORCID: https://orcid.org/0000-0002-0685-4862)
- W.H. Wilson Tang (ORCID: https://orcid.org/0000-0002-8335-735X)
- Mardi Gomberg‐Maitland (ORCID: https://orcid.org/0000-0003-0482-4560)
- Milena Radeva (ORCID: https://orcid.org/0000-0002-8057-4244)
- John B. Cadigan
- David J. Brady (ORCID: https://orcid.org/0000-0001-5655-2478)
- Jamie E. Newman (ORCID: https://orcid.org/0000-0001-8880-8132)
- Johannes Roth (ORCID: https://orcid.org/0000-0002-6109-1503)
- Jennifer Haythe (ORCID: https://orcid.org/0000-0003-3506-5157)
- Laurie Lawler
- R Sutliff
- Louise A. Durst
- J. MacKrell
- Christine Jellis (ORCID: https://orcid.org/0000-0002-8610-0533)
- Catherine E. Simpson (ORCID: https://orcid.org/0000-0002-2388-5660)
- Robert E. Weiss (ORCID: https://orcid.org/0000-0003-3648-8522)
- Ju Youn Kim
- Harold Erickson (ORCID: https://orcid.org/0000-0002-9104-8987)
- Steven Hsu (ORCID: https://orcid.org/0000-0002-8384-2638)
- Evelyn M. Horn (ORCID: https://orcid.org/0000-0002-5751-9415)
- Elizabeth Joseloff
- Jonathan W. Weinsaft (ORCID: https://orcid.org/0000-0002-8386-0297)
- Monica Mukherjee (ORCID: https://orcid.org/0000-0001-6088-0773)
- André Terzic (ORCID: https://orcid.org/0000-0001-9210-009X)
- Samar Farha (ORCID: https://orcid.org/0000-0003-4800-8928)
- Aiden Abidov (ORCID: https://orcid.org/0000-0002-8230-7406)
- Ryan J. Tedford (ORCID: https://orcid.org/0000-0001-9045-7722)
- Jeanne K. Drinko
- Todd M. Kolb (ORCID: https://orcid.org/0000-0003-0524-7400)
- Sharon Rounds (ORCID: https://orcid.org/0000-0002-5008-616X)
- Joe G. N. Garcia (ORCID: https://orcid.org/0000-0002-6934-0420)
- Jason Thomas (ORCID: https://orcid.org/0000-0003-3892-7197)
- Mitchell A. Olman (ORCID: https://orcid.org/0000-0003-3262-3598)
- Anna R. Hemnes (ORCID: https://orcid.org/0000-0002-2755-5845)
- Michelle L. Ricketts
- Thomas A. Foley (ORCID: https://orcid.org/0000-0003-0347-7931)
- Irina Sobol (ORCID: https://orcid.org/0000-0002-1328-3447)
- Darin Rosen (ORCID: https://orcid.org/0009-0001-5352-9288)
- Kristi Rohwer
- Jane A. Leopold (ORCID: https://orcid.org/0000-0003-0598-8882)
- Ting‐Tse Lin (ORCID: https://orcid.org/0000-0002-8810-5127)
- Kevin McCarthy (ORCID: https://orcid.org/0000-0001-9317-5624)
- S Yu
- Harsimran Singh (ORCID: https://orcid.org/0000-0001-6645-3115)
- Bo Hu (ORCID: https://orcid.org/0000-0001-8601-8284)
- Francesco Di Filippo (ORCID: https://orcid.org/0000-0002-4727-8953)
- Franz Rischard (ORCID: https://orcid.org/0000-0002-6861-8304)
- R Vanderpool
- Nicholas S. Hill (ORCID: https://orcid.org/0000-0002-8242-8339)
- Lei Gao (ORCID: https://orcid.org/0000-0003-1476-1460)
- Tang WHW
- Maria Karas (ORCID: https://orcid.org/0000-0002-8763-6460)
- Kyle A. Carey (ORCID: https://orcid.org/0000-0002-5038-6074)
- Lisa Postow
- Stefan L. Zimmerman (ORCID: https://orcid.org/0000-0002-9422-6742)
- S.C. Mathai (ORCID: https://orcid.org/0009-0008-8769-7694)
- Kerri L. Wiggins (ORCID: https://orcid.org/0000-0003-2749-1279)
- M Park
- Benjamin R. Gochanour
- Alexandra C. Racanelli (ORCID: https://orcid.org/0000-0002-8414-097X)
- Robert P. Frantz (ORCID: https://orcid.org/0000-0003-4128-3978)
- B Maron
- Margaret Park (ORCID: https://orcid.org/0000-0003-4074-8630)
- Raymond L. Benza (ORCID: https://orcid.org/0000-0001-9627-6236)
- David A. Kass (ORCID: https://orcid.org/0000-0003-1596-2299)
- Jeffrey Fessel (ORCID: https://orcid.org/0000-0002-6772-3348)
- Wael A. Jaber (ORCID: https://orcid.org/0000-0001-5642-2112)
- Gabriele Grünig (ORCID: https://orcid.org/0000-0002-1846-6322)
- S.A.A. Comhair
- Xuefei Tian (ORCID: https://orcid.org/0000-0003-4235-0896)
- T. Sands (ORCID: https://orcid.org/0000-0001-9718-6515)
- Geoffrey Bergman (ORCID: https://orcid.org/0000-0001-9640-3813)
- Jane Wilcox
- Christopher G. Scott (ORCID: https://orcid.org/0000-0003-1340-0647)
- Maite Velázquez Martín (ORCID: https://orcid.org/0000-0002-0303-0796)
- Yongping Fu (ORCID: https://orcid.org/0000-0003-0648-3704)
- David M. Systrom (ORCID: https://orcid.org/0000-0002-9610-6330)
- R Nawabit
- Kewal Asosingh
- Erika B. Rosenzweig (ORCID: https://orcid.org/0000-0003-4849-214X)
- Reena Mehra (ORCID: https://orcid.org/0000-0002-6222-2675)
- Xiaotian Li (ORCID: https://orcid.org/0000-0002-2051-4581)
- Akshay S. Desai (ORCID: https://orcid.org/0000-0002-1443-0701)
- Minghui Li (ORCID: https://orcid.org/0000-0002-0880-2783)
- Sanni Yaya (ORCID: https://orcid.org/0000-0002-6003-139X)
- Todd Bull (ORCID: https://orcid.org/0009-0003-6221-7790)
- R Renapurkar
- Gerald J. Beck (ORCID: https://orcid.org/0000-0002-8876-5045)
- Meredith E. Pugh
- David A. Payne
- C.S. Lim
- David K. Menon
- D. Neumann
- Richard B. Devereux
- Heinz Brock
- Rachel D’Amico
- A Borowski
- K Wadih
- K Bastert
- H Halbach
Institutions
- Tufts University (US)
- Brigham and Women's Hospital (US)
- Cleveland Clinic (US)
- Westchester Medical Center (US)
- University of Arizona (US)
- Johns Hopkins University (US)
- University of Miami (US)
- Medical University of South Carolina (US)
- New York Medical College (US)
- Vanderbilt University (US)
- Cornell University (US)
- University of Washington Medical Center (US)
- WinnMed (US)
- University Medical Center (US)
- Cleveland Clinic Lerner College of Medicine (US)
- University Hospital and Clinics (US)
- New York University (US)
Publication Details
- Journal
- Journal of the American Heart Association
- Published
- 2025-05-22
- DOI
- https://doi.org/10.1161/jaha.124.041127
- Citations
- 4
- Primary Topic
- Pulmonary Hypertension Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 6.07