Kynurenine pathway metabolism evolves with development of preclinical and scleroderma-associated pulmonary arterial hypertension-Reference-Cited by-同舟云学术

Kynurenine pathway metabolism evolves with development of preclinical and scleroderma-associated pulmonary arterial hypertension

Published:2023-11-01 Issue:5 Volume:325 Page:L617-L627
ISSN:1040-0605
Container-title:American Journal of Physiology-Lung Cellular and Molecular Physiology
language:en
Short-container-title:American Journal of Physiology-Lung Cellular and Molecular Physiology

Author:

Simpson Catherine E.¹^ORCID,Ambade Anjira S.¹,Harlan Robert²,Roux Aurelie²^ORCID,Aja Susan²,Graham David²,Shah Ami A.³,Hummers Laura K.³,Hemnes Anna R.⁴,Leopold Jane A.⁵,Horn Evelyn M.⁶,Berman-Rosenzweig Erika S.⁷,Grunig Gabriele⁸,Aldred Micheala A.⁹^ORCID,Barnard John¹⁰,Comhair Suzy A. A.¹⁰,Tang W. H. Wilson¹¹,Griffiths Megan¹²,Rischard Franz¹³,Frantz Robert P.¹⁴,Erzurum Serpil C.¹⁰^ORCID,Beck Gerald J.¹⁰,Hill Nicholas S.¹⁵^ORCID,Mathai Stephen C.¹,Hassoun Paul M.¹^ORCID,Damico Rachel L.¹,

Affiliation:

1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States

2. Johns Hopkins All Children’s Molecular Determinants Core, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, United States

3. Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

4. Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States

5. Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States

6. Division of Cardiology, Department of Medicine, Cornell University Medical Center, New York, New York, United States

7. Division of Pediatric Cardiology, Columbia University Medical Center/NewYork-Presbyterian Hospital, New York, New York, United States

8. Divisions of Environmental and Pulmonary Medicine, Department of Medicine, NYU Grossman School of Medicine, New York, New York, United States

9. Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States

10. Department of Inflammation and Immunity, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, United States

11. Division of Heart Failure and Transplant Medicine, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, United States

12. Division of Pediatric Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States

13. Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Arizona College of Medicine, Tucson, Arizona, United States

14. Division of Circulatory Failure, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, United States

15. Pulmonary, Critical Care and Sleep Division, Tufts University, Boston, Massachusetts, United States

Abstract

Our study shows an early increase in kynurenine pathway metabolism in at-risk subjects with systemic sclerosis who develop pulmonary arterial hypertension (PAH). We show that kynurenine pathway upregulation precedes clinical diagnosis and that this metabolic shift is associated with increased disease severity and shorter survival times. We also show that gene expression of TDO2, an enzyme that generates kynurenine from tryptophan, rises with PAH development.

Funder

Johns Hopkins inHealth Initiative

Donald B. and Dorothy L. Stabler Foundation

Nancy and Joachim Bechtle Precision Medicine Fund for Scleroderma

Manugian Family Scholar

HHS | NIH | National Heart, Lung, and Blood Institute

National Scleroderma Foundation

Pulmonary Hypertension Association

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology