Evidence map›Paper›PMID 42214135›Full record

ArticleJACC. Basic to translational science2026

Impaired Lung BCAA Metabolism Promotes Ferroptosis and Resultant Pulmonary Arterial Hypertension-Associated Hepatopathy.

Madelyn J Blake, Jason Hong, Adam Brownstein, Christopher J Rhodes, Emilia M Swietlik, Jeffrey C Blake, Ryan A Moon, Lynn M Hartweck, Jenna B Mendelson, Sasha Z Prisco and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JACC. Basic to translational science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Madelyn J BlakeGazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
Jason HongDivision of Pulmonary and Critical Care Medicine, University of California, Los Angeles, California, USA.
Adam BrownsteinDivision of Pulmonary and Critical Care Medicine, University of California, Los Angeles, California, USA.
Christopher J RhodesNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Emilia M SwietlikAddenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; University of Warmia and Mazury, Olsztyn, Poland.
Jeffrey C BlakeCardiovascular Division, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota, USA.
Ryan A MoonCardiovascular Division, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota, USA.
Lynn M HartweckCardiovascular Division, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota, USA.
Jenna B MendelsonCardiovascular Division, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota, USA.
Sasha Z PriscoCardiovascular Division, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota, USA.
Todd MarkowskiCenter for Metabolomics and Proteomics, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
LeeAnn HigginsCenter for Metabolomics and Proteomics, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
Kevin MurrayCenter for Metabolomics and Proteomics, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
Candance GuerreroCenter for Metabolomics and Proteomics, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
Sandra Breuils-BonnetDepartment of Medicine, Université Laval, Québec, Canada.
Steeve ProvencherDepartment of Medicine, Université Laval, Québec, Canada.
Joanna Pepke-ZabaPapworth NHS Foundation, Cambridge, United Kingdom.
Mark ToshnerPapworth NHS Foundation, Cambridge, United Kingdom; Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
Martin WilkinsNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Sebastien BonnetDepartment of Medicine, Université Laval, Québec, Canada.
Kurt W PrinsGazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA. Electronic address: prins@musc.edu.

Funding

GP130 Antagonism in Porcine RV Pressure OverloadR01HL162927 · NHLBI · UNIVERSITY OF MINNESOTA · PI Kurt W Prins · 2022 to 2026
$3.3M
Multi-scale Investigation of Sex Differences in Right Ventricular Function via Estrogen-Microtubule InteractionsR01HL158795 · NHLBI · UNIVERSITY OF MINNESOTA · PI Kurt W Prins · 2022 to 2026
$2.8M
NHLBI NIH HHS R01 HL158795NHLBI NIH HHS R01 HL162927
6 · The paper itself

Abstract

Dysregulated branched-chain amino acid (BCAA) metabolism occurs in pulmonary arterial hypertension (PAH), but its role in pulmonary vascular disease and resultant hepatopathy remains undefined. Here, human metabolomic and transcriptomic analyses identified altered BCAA homeostasis and deficits in BCAA catabolic and ferroptosis pathways in PAH pulmonary artery smooth muscle cells (PASMCs). In vitro, excess BCAAs promoted a pro-ferroptotic phenotype in human PASMCs. In monocrotaline-induced PAH, pharmacologic activation of BCAA catabolism with BT2 reduced disease severity, improved right ventricular function, and enhanced exercise capacity while reversing lung ferroptotic signatures and perivascular complement deposition. BT2 also mitigated hepatic shear stress phenotypes, including hepatocyte nuclear expansion and mitochondrial protein dysregulation. Human PAH livers recapitulated many of the hepatic shear stress phenotypes including nuclear expansion and metabolic alterations. These data implicate impaired BCAA metabolism as a driver of PAH via PASMC ferroptosis and potentially link PAH to hepatic metabolic dysfunction through mechanical stress-associated pathways.

Indexed as

branched-chain amino acidsferroptosishepatopathypulmonary arterial hypertensionright ventricular failure

Identifiers

PMID42214135
PMCPMC13241934

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.