ArticleCell metabolism2022
Extra-cardiac BCAA catabolism lowers blood pressure and protects from heart failure.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06645769 (Na-Phenylbutyrate VAscular Trial), which is not on this map. Cited by 73 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
7.4field-weighted citation impact, top 2% of its field
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.
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.
NCT06645769 early_phase1not yet recruitingnot on this mapstarted 2027, after this paper: background citation
Na-Phenylbutyrate VAscular Trial
Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Causal Relationship Between Branched-Chain Amino Acids and Hypertension: A Mendelian Randomization Study.Journal of the American Heart Association · 2024Pooled it
- Roles of inflammation and metabolic dysfunction in cardiovascular diseases: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Co-Enrichment ofInternational journal of molecular sciences · 2026Article
- BCKDK protects against obesity-induced cardiac remodelling and dysfunction by alleviating mitochondrial oxidative stress and ROS-driven MAPK signalling.Redox biology · 2026Article
- Commentary: Unveiling a Metabolic-Lymphatic Axis in the Pathogenesis of Heart Failure With Preserved Ejection Fraction.Cardiology discovery · 2026Article
- Fueling fibrosis: BCAT1 links branched-chain amino acid metabolism to collagen production.The Journal of clinical investigation · 2026Article
- Exercise and Fat: A Primer.Sports medicine - open · 2026Review
- Analysis of serum NMR metabolomics in fibrotic diseases of the myocardium.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Divergent skeletal muscle metabolite exchange in insulin-like growth factor-1-stimulated myotubes and resistance-exercised human muscle.Experimental physiology · 2026Article
- ACAD8 deficiency promotes pathological cardiac hypertrophy in response to pressure overload by regulating histone isobutyrylation.Nature communications · 2026Article
- Dietary intake and BCAA metabolism regulate pulmonary fibrosis through KDM4A-mediated epigenetic remodeling in male mice.Nature communications · 2026Article
- GRSF1 Protects Against Heart Failure by Maintaining BCAA Homeostasis.Circulation · 2026Article
- BCAA Metabolic Dyshomeostasis in Cardiovascular Disease: Pathogenic Mechanisms and Intervention.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2026Review
- Targeting the metabolic fingerprint of amino acids to identify novel metabolic characteristics in osteosarcoma patients undergoing anthracycline treatment.Scientific reports · 2026Article
- Environmental Amino Acid Sensing Regulates the Rate of ASC Translation and NLRP3 Inflammasome Assembly.bioRxiv : the preprint server for biology · 2026Article
- Article
- Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF.International journal of molecular sciences · 2026Review
- Vascular Smooth Muscle Cell-Specific BCAT2 Deficiency Attenuates Diabetic Atherosclerotic Calcification via Histone Propionylation.Research (Washington, D.C.) · 2026Article
- Artificial intelligence-driven design and optimization of mitochondria-targeted nanocarriers for chronic heart failure.Frontiers in bioengineering and biotechnology · 2026Review
- Branched-chain amino acids from plants and the metabolic syndrome: pathways and pharmacological applications.Frontiers in nutrition · 2026Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 6 institutions in 2 countries.
Danielle MurashigeDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Jae Woo JungDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Michael D NeinastDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Ludwig Institute for Cancer Research, Princeton Branch, Princeton, NJ 08544, USA.
Michael G LevinDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Qingwei ChuDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Jonathan P LambertCardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Joanne F GarbinciusCardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Boa KimDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Atsushi HoshinoDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Ingrid Marti-PamiesDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Kendra S McDaidDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Swapnil V ShewaleDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Emily FlamDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Steven YangDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Emilia RobertsDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Li LiDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Michael P MorleyDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Kenneth C BediDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Matthew C HymanDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
David S FrankelDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Kenneth B MarguliesDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Richard K AssoianDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
John W ElrodCardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Cholsoon JangLudwig Institute for Cancer Research, Princeton Branch, Princeton, NJ 08544, USA; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Joshua D RabinowitzLudwig Institute for Cancer Research, Princeton Branch, Princeton, NJ 08544, USA.
Zoltan AranyDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: zarany@pennmedicine.upenn.edu.
University of Pennsylvania · USTemple University · USPrinceton University · USKyoto Prefectural University of Medicine · JPLudwig Cancer Research · USWashington University in St. Louis · US
Funding
VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI DOUGLAS J EPSTEIN · 1986 to 2026
$48.3MTraining Program in Cardiovascular Biology and MedicineT32HL007843 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI THOMAS P. CAPPOLA, Sharlene M Day · 1996 to 2026
$11.0MMultidisciplinary Training in Cardiovascular BiologyT32HL007954 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DAVIES, PETER FRANCIS · 2000 to 2019
$9.9MIntegrative genomics of human heart failureR01HL105993 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ASHLEY, EUAN A, CAPPOLA, THOMAS P. · 2011 to 2014
$8.9MKeeping fat out of muscle - Role of Branched Amino AcidsAmino Acids in Insulin ResistanceR01DK114103 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Zoltan P Arany · 2018 to 2026
$4.5MMechanical Stress-Dependent Remodeling of the Cardiac Microtubule NetworkR01HL149891 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Kenneth Ber Margulies, Benjamin Lears Prosser · 2020 to 2026
$4.2MBranched chain amino acids in heart failureR01HL152446 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Zoltan P Arany · 2020 to 2026
$3.7MBranched chain amino acids in pancreatic carcinogenesisR01CA248315 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Zoltan P Arany, Kathryn Elaine Wellen · 2020 to 2026
$2.8MArterial stiffening and SMC mechanobiology in Hutchinson-Guilford Progeria SyndromeR01AG062140 · NIA · UNIVERSITY OF PENNSYLVANIA · PI ASSOIAN, RICHARD · 2019 to 2023
$2.0MPost-doctoral Training Program in Cancer Metabolism and Tumor-host InteractionsT32CA257957 · NCI · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI KANG, YIBIN, ZONG, WEI-XING · 2021 to 2025
$1.2MIndirect calorimetry cages equipped for glucose and blood pressure telemetryS10OD025098 · OD · UNIVERSITY OF PENNSYLVANIA · PI BAUR, JOSEPH A. · 2019 to 2019
$750kMolecular modulation of the mitochondrial Na+/Ca2+ exchanger as a novel therapeutic target for heart failure.F32HL151146 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI GARBINCIUS, JOANNE FRANCES · 2020 to 2021
$134kNCI NIH HHS R01 CA248315NCI NIH HHS T32 CA257957NHLBI NIH HHS F30 HL142186NHLBI NIH HHS F32 HL151146NHLBI NIH HHS R01 HL105993NHLBI NIH HHS R01 HL149891NHLBI NIH HHS R01 HL152446NHLBI NIH HHS T32 HL007843NHLBI NIH HHS T32 HL007954NIA NIH HHS R01 AG062140NIDDK NIH HHS P30 DK019525NIDDK NIH HHS R01 DK114103NIH HHS S10 OD025098
Abstract
Pharmacologic activation of branched-chain amino acid (BCAA) catabolism is protective in models of heart failure (HF). How protection occurs remains unclear, although a causative block in cardiac BCAA oxidation is widely assumed. Here, we use in vivo isotope infusions to show that cardiac BCAA oxidation in fact increases, rather than decreases, in HF. Moreover, cardiac-specific activation of BCAA oxidation does not protect from HF even though systemic activation does. Lowering plasma and cardiac BCAAs also fails to confer significant protection, suggesting alternative mechanisms of protection. Surprisingly, activation of BCAA catabolism lowers blood pressure (BP), a known cardioprotective mechanism. BP lowering occurred independently of nitric oxide and reflected vascular resistance to adrenergic constriction. Mendelian randomization studies revealed that elevated plasma BCAAs portend higher BP in humans. Together, these data indicate that BCAA oxidation lowers vascular resistance, perhaps in part explaining cardioprotection in HF that is not mediated directly in cardiomyocytes.
Indexed as
Amino Acids, Branched-ChainHeart FailureBlood PressureEnergy MetabolismHeartHumansAmino Acids, Branched-ChainBCAAblood pressurebranched-chain amino acidcardiac metabolismcardiovascular metabolismheart failurehypertensionMendelian randomizationmetabolomics
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
NCT06645769ClinicalTrials.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.