ArticleJournal of the American Heart Association2019
Therapeutic Effect of Targeting Branched-Chain Amino Acid Catabolic Flux in Pressure-Overload Induced Heart Failure.
Article in Journal of the American Heart Association, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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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.
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Who cites it
50 citing papers in PubMed, 77 citations in OpenAlex.
- A randomized placebo-controlled clinical trial for pharmacological activation of BCAA catabolism in patients with type 2 diabetes.Nature communications · 2022Trial
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- The L-type amino acid transporter inhibitor, BCH, inhibits myotube BCAA uptake and mitochondrial function without altering myotube insulin sensitivity during insulin resistance in C2C12 myotubes.Acta diabetologica · 2026Article
- Early branched-chain amino acid reduction delays the onset of cognitive decline in a mouse model of Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Article
- Cardiac intermediary metabolism in heart failure: substrate use, signalling roles and therapeutic targets.Nature reviews. Cardiology · 2025Review
- Branched-Chain Amino Acids in Parkinson's Disease: Molecular Mechanisms and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Off-target depletion of plasma tryptophan by allosteric inhibitors of BCKDK.Molecular metabolism · 2025Article
- Emerging Insights into the Relationship Between Amino Acid Metabolism and Diabetic Cardiomyopathy.Biomolecules · 2025Review
- Impaired cardiac branched-chain amino acid metabolism in a novel model of diabetic cardiomyopathy.Cardiovascular diabetology · 2025Article
- Dietary Branched-Chain Amino Acids Modify Postinfarct Cardiac Remodeling and Function in the Murine Heart.Journal of the American Heart Association · 2025Article
- Branched-chain amino acids and insulin resistance in type 2 diabetes: from metabolic dysregulation to therapeutic targets.Frontiers in endocrinology · 2025Review
- BCAA catabolism targeted therapy for heart failure with preserved ejection fraction.Theranostics · 2025Article
- Activation of branched chain amino acid catabolism protects against nephrotoxic acute kidney injury.American journal of physiology. Renal physiology · 2025Article
- Anaplerotic filling in heart failure: a review of mechanism and potential therapeutics.Cardiovascular research · 2024Review
- Advances in myocardial energy metabolism: metabolic remodelling in heart failure and beyond.Cardiovascular research · 2024Review
- Dietary Branched Chain Amino Acids Modify Post-Infarct Cardiac Remodeling and Function in the Murine Heart.bioRxiv : the preprint server for biology · 2024Article
- The role of BCAA metabolism in metabolic health and disease.Experimental & molecular medicine · 2024Review
- Effect of mTORC Agonism via MHY1485 with and without Rapamycin on C2C12 Myotube Metabolism.International journal of molecular sciences · 2024Article
- Duality of Branched-Chain Amino Acids in Chronic Cardiovascular Disease: Potential Biomarkers versus Active Pathophysiological Promoters.Nutrients · 2024Review
- Advances in Metabolic Remodeling and Intervention Strategies in Heart Failure.Journal of cardiovascular translational research · 2024Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Background Branched-chain amino acid (BCAA) catabolic defect is an emerging metabolic hallmark in failing hearts in human and animal models. The therapeutic impact of targeting BCAA catabolic flux under pathological conditions remains understudied. Methods and Results BT2 (3,6-dichlorobenzo[b]thiophene-2-carboxylic acid), a small-molecule inhibitor of branched-chain ketoacid dehydrogenase kinase, was used to enhance BCAA catabolism. After 2 weeks of transaortic constriction, mice with significant cardiac dysfunctions were treated with vehicle or BT2. Serial echocardiograms showed continuing pathological deterioration in left ventricle of the vehicle-treated mice, whereas the BT2-treated mice showed significantly preserved cardiac function and structure. Moreover, BT2 treatment improved systolic contractility and diastolic mechanics. These therapeutic benefits appeared to be independent of impacts on left ventricle hypertrophy but associated with increased gene expression involved in fatty acid utilization. The BT2 administration showed no signs of apparent toxicity. Conclusions Our data provide the first proof-of-concept evidence for the therapeutic efficacy of restoring BCAA catabolic flux in hearts with preexisting dysfunctions. The BCAA catabolic pathway represents a novel and potentially efficacious target for treatment of heart failure.
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Registered trials
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.