ArticleAmerican journal of physiology. Lung cellular and molecular physiology2023
Kynurenine pathway metabolism evolves with development of preclinical and scleroderma-associated pulmonary arterial hypertension.
Registry-linked trialOpen access · greenAbstract read
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Article in American journal of physiology. Lung cellular and molecular physiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04071327 (Pulmonary Hypertension Association Registry), which is not on this map. Cited by 20 papers.
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0cells of the map it votes in
20citing papers in PubMed
6.4field-weighted citation impact, top 3% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pulmonary Hypertension Association Registry
Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Divergent Inflammatory and Bioenergetic Metabolomic Signatures Distinguish Methamphetamine-Associated From Idiopathic Pulmonary Arterial Hypertension.Pulmonary circulation · 2026Article
- Cardiometabolic reprogramming in pulmonary arterial hypertension: Implications for right ventricular dysfunction and therapeutic strategies.Chinese herbal medicines · 2026Review
- Metabolomic Network Analysis Reveals Reorganization of Lipid and Steroid Programs Linked to Right Ventricular-Pulmonary Vascular Function in Pulmonary Hypertension.bioRxiv : the preprint server for biology · 2026Article
- Increased Xanthine Oxidoreductase Activity in Patients With Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.CHEST pulmonary · 2026Article
- Tryptophan metabolism: a potential link between the gut microbiota and pulmonary vascular remodeling in pulmonary hypertension.Frontiers in cellular and infection microbiology · 2026Review
- The gut microbiota-aromatic amino acid axis in cardiovascular disease: pathophysiological roles, translational biomarkers, and therapeutic targeting.Frontiers in cardiovascular medicine · 2026Review
- The NOTCH3 extracellular domain is a serum biomarker for pulmonary arterial hypertension.Nature medicine · 2026Article
- Rewriting the vascular script: epigenetic modifiers as scribes of metabolic reprogramming in pulmonary hypertension.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Metabolomic Evidence of Biological Overlap with Heart Failure with Preserved Ejection Fraction in a Subset of Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2025Article
- Metabolomic Evidence of Biological Overlap with Heart Failure with Preserved Ejection Fraction in a Subset of Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2025Article
- IDO-1 Promotes Pulmonary Vascular Remodeling Via Kynurenine Pathway in Pulmonary Arterial Hypertension.Journal of the American Heart Association · 2025Article
- Serum Metabolomic Profiling Reveals Differences Between Systemic Sclerosis Patients with Polyneuropathy.International journal of molecular sciences · 2025Article
- IDO-Dependent Tryptophan Metabolites and Endocan as Effective Diagnostic Biomarkers for Pregnancy with Pulmonary Hypertension.International journal of women's health · 2025Article
- Perturbations of tryptophan catabolism via the kynurenine pathway are associated with stage 2 postoperative outcomes in single ventricle heart disease.Physiological reports · 2024Article
- Metabolomics in systemic sclerosis.Rheumatology international · 2024Review
- Aberrant long-chain fatty acid metabolism associated with evolving systemic sclerosis-associated pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Observational
- Circulating Biomarkers in Pulmonary Arterial Hypertension: An Update.Biomolecules · 2024Review
- Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: From Bedside to Bench and Back Again.International journal of molecular sciences · 2024Review
- Different Kynurenine Pathway Dysregulation in Systemic Sclerosis in Men and Women.International journal of molecular sciences · 2024Article
- Gut microbiome and metabolomics in systemic sclerosis: feature, link and mechanisms.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
27 authors at 13 institutions in 1 country.
Catherine E SimpsonDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States.ORCID 0000-0002-2388-5660
Anjira S AmbadeDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States.
Robert HarlanJohns Hopkins All Children's Molecular Determinants Core, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, United States.
Aurelie RouxJohns Hopkins All Children's Molecular Determinants Core, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, United States.ORCID 0000-0001-5579-001X
Susan AjaJohns Hopkins All Children's Molecular Determinants Core, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, United States.
David GrahamJohns Hopkins All Children's Molecular Determinants Core, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, United States.
Ami A ShahDivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Laura K HummersDivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Anna R HemnesDivision of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States.
Jane A LeopoldDivision of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States.
Evelyn M HornDivision of Cardiology, Department of Medicine, Cornell University Medical Center, New York, New York, United States.
Erika S Berman-RosenzweigDivision of Pediatric Cardiology, Columbia University Medical Center/NewYork-Presbyterian Hospital, New York, New York, United States.
Gabriele GrunigDivisions of Environmental and Pulmonary Medicine, Department of Medicine, NYU Grossman School of Medicine, New York, New York, United States.
Micheala A AldredDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States.ORCID 0000-0002-7390-9181
John BarnardDepartment of Inflammation and Immunity, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, United States.
Suzy A A ComhairDepartment of Inflammation and Immunity, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, United States.
W H Wilson TangDivision of Heart Failure and Transplant Medicine, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, United States.
Megan GriffithsDivision of Pediatric Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States.
Franz RischardDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Arizona College of Medicine, Tucson, Arizona, United States.
Robert P FrantzDivision of Circulatory Failure, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, United States.
Serpil C ErzurumDepartment of Inflammation and Immunity, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, United States.ORCID 0000-0001-5202-9065
Gerald J BeckDepartment of Inflammation and Immunity, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, United States.
Nicholas S HillPulmonary, Critical Care and Sleep Division, Tufts University, Boston, Massachusetts, United States.ORCID 0000-0002-8242-8339
Stephen C MathaiDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States.
Paul M HassounDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States.ORCID 0000-0003-0601-4975
Rachel L DamicoDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States.
the PVDOMICS Study Group
Johns Hopkins University · USCleveland Clinic Lerner College of Medicine · USBrigham and Women's Hospital · USCleveland Clinic · USCornell University · USIndiana University School of MedicineMayo Clinic · USNewYork–Presbyterian Hospital · USNew York University · USThe University of Texas Southwestern Medical Center · USTufts University · USUniversity of Arizona · USVanderbilt University · US
Funding
Pulmonary Vascular Disease Phenomics Program (PVDOMICS) Data Coordinating CenterU01HL125177 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BECK, GERALD J, ERZURUM, SERPIL C. · 2014 to 2020
$20.0MGenomics of Pulmonary Vascular DiseaseR35HL140019 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI ALDRED, MICHEALA A · 2018 to 2024
$5.6MFunctional Impact of Col18a1/Endostatin Variants in PAHR01HL132153 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI DAMICO, RACHEL L, HASSOUN, PAUL M. · 2017 to 2020
$2.5MIntergrated Endothelial Phenotyping to Redefine Pulmonary HypertensionU01HL125215 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LEOPOLD, JANE A, WAXMAN, AARON B · 2014 to 2018
$1.7MPVDOMICS Defining the Future Fingerprints of Pulmonary Vascular DiseaseU01HL125218 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BERMAN-ROSENZWEIG, ERIKA S., HORN, EVELYN · 2014 to 2018
$1.6MRedefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics: Clinical Centers (CC) (U01).U01HL125205 · NHLBI · MAYO CLINIC ROCHESTER · PI FRANTZ, ROBERT PAUL · 2014 to 2018
$1.5MA molecular phenotype of combined pulmonary hypertensionU01HL125212 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI HEMNES, ANNA R, NEWMAN, JOHN HUGHES · 2014 to 2018
$1.5MPhenomic and genomic study to subphenotype Hispanics with pulmonary hypertensionU01HL125208 · NHLBI · UNIVERSITY OF ARIZONA · PI GARCIA, JOE G. N., RISCHARD, FRANZ P · 2014 to 2018
$1.5MHopkins Clinical Center for Pulmonary Vascular Disease Phenomics ProgramU01HL125175 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI HASSOUN, PAUL M., MATHAI, STEPHEN C · 2015 to 2019
$1.1MThe role of xanthine oxidoreductase activity and altered metabolism in scleroderma-associated pulmonary arterial hypertensionK23HL153781 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI SIMPSON, CATHERINE · 2020 to 2024
$883kNHLBI NIH HHS K23 HL153781NHLBI NIH HHS R01 HL132153NHLBI NIH HHS R35 HL140019NHLBI NIH HHS U01 HL125175NHLBI NIH HHS U01 HL125177NHLBI NIH HHS U01 HL125205NHLBI NIH HHS U01 HL125208NHLBI NIH HHS U01 HL125212NHLBI NIH HHS U01 HL125215NHLBI NIH HHS U01 HL125218
Abstract
Understanding metabolic evolution underlying pulmonary arterial hypertension (PAH) development may clarify pathobiology and reveal disease-specific biomarkers. Patients with systemic sclerosis (SSc) are regularly surveilled for PAH, presenting an opportunity to examine metabolic change as disease develops in an at-risk cohort. We performed mass spectrometry-based metabolomics on longitudinal serum samples collected before and near SSc-PAH diagnosis, compared with time-matched SSc subjects without PAH, in a SSc surveillance cohort. We validated metabolic differences in a second cohort and determined metabolite-phenotype relationships. In parallel, we performed serial metabolomic and hemodynamic assessments as the disease developed in a preclinical model. For differentially expressed metabolites, we investigated corresponding gene expression in human and rodent PAH lungs. Kynurenine and its ratio to tryptophan (kyn/trp) increased over the surveillance period in patients with SSc who developed PAH. Higher kyn/trp measured two years before diagnostic right heart catheterization increased the odds of SSc-PAH diagnosis (OR 1.57, 95% CI 1.05-2.36,
Indexed as
Hypertension, PulmonaryPulmonary Arterial HypertensionScleroderma, SystemicBiomarkersFamilial Primary Pulmonary HypertensionHumansKynurenineTryptophanBiomarkersKynurenineTryptophanbiomarkersmetabolomicspulmonary arterial hypertension
Identifiers
What OpenQuestion holds
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Read underepoch 390
Registered trials
NCT04071327ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.