ArticleActa pharmacologica Sinica2023
Cell-autonomous effect of cardiomyocyte branched-chain amino acid catabolism in heart failure in mice.
Article in Acta pharmacologica Sinica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 22 citations in OpenAlex.
- Roles of inflammation and metabolic dysfunction in cardiovascular diseases: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- BCKDK protects against obesity-induced cardiac remodelling and dysfunction by alleviating mitochondrial oxidative stress and ROS-driven MAPK signalling.Redox biology · 2026Article
- Hundreds of cardiac MRI traits derived using 3D diffusion autoencoders share a common genetic architecture.Nature communications · 2026Article
- ACAD8 deficiency promotes pathological cardiac hypertrophy in response to pressure overload by regulating histone isobutyrylation.Nature communications · 2026Article
- BCAA Metabolic Dyshomeostasis in Cardiovascular Disease: Pathogenic Mechanisms and Intervention.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2026Review
- Leucine-Dependent SLC7A5-PGAM5 Interaction Promotes Advanced Atherosclerosis Through Hindering Mitochondrial Function of Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolic reprogramming in cardiac fibrosis: mechanisms, crosstalk, and therapeutic interventions.Frontiers in physiology · 2026Review
- Multimodal Therapeutic Strategies Targeting BCAA Metabolism in Diabetic Cardiomyopathy: A Path to Cardioprotection.Cardiovascular toxicology · 2025Review
- Empagliflozin enhances metabolic efficiency and improves left ventricular hypertrophy in a hypertrophic cardiomyopathy mouse model.European heart journal · 2025Article
- Metabolic regulation for the treatment of ischemic heart disease with stem cells and extracellular vesicles.NPJ cardiovascular health · 2025Review
- Cardiac intermediary metabolism in heart failure: substrate use, signalling roles and therapeutic targets.Nature reviews. Cardiology · 2025Review
- The regulatory role of exercise in heart failure and myocardial energy metabolism: A review.Biomolecules & biomedicine · 2025Review
- Recent Advances and Perspectives of Metabolomics-Based Investigations in Coronary Heart Disease.Current atherosclerosis reports · 2025Review
- Caprylic Acid Restores Branched-Chain Amino Acid Metabolism in a Mouse Cachexia Model.Current issues in molecular biology · 2025Article
- BCAA catabolism targeted therapy for heart failure with preserved ejection fraction.Theranostics · 2025Article
- Role of AMP deaminase in diabetic cardiomyopathy.Molecular and cellular biochemistry · 2024Review
- Glucagon Receptor Antagonist for Heart Failure With Preserved Ejection Fraction.Circulation research · 2024Article
- Duality of Branched-Chain Amino Acids in Chronic Cardiovascular Disease: Potential Biomarkers versus Active Pathophysiological Promoters.Nutrients · 2024Review
- Circulating Branched Chain Amino Acids and Cardiometabolic Disease.Journal of the American Heart Association · 2024Review
- The Role of Branched-chain Amino Acids and Their Metabolism in Cardiovascular Diseases.Journal of cardiovascular translational research · 2024Review
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 3 countries.
Funding
Abstract
Parallel to major changes in fatty acid and glucose metabolism, defect in branched-chain amino acid (BCAA) catabolism has also been recognized as a metabolic hallmark and potential therapeutic target for heart failure. However, BCAA catabolic enzymes are ubiquitously expressed in all cell types and a systemic BCAA catabolic defect is also manifested in metabolic disorder associated with obesity and diabetes. Therefore, it remains to be determined the cell-autonomous impact of BCAA catabolic defect in cardiomyocytes in intact hearts independent from its potential global effects. In this study, we developed two mouse models. One is cardiomyocyte and temporal-specific inactivation of the E1α subunit (BCKDHA-cKO) of the branched-chain α-ketoacid dehydrogenase (BCKDH) complex, which blocks BCAA catabolism. Another model is cardiomyocyte specific inactivation of the BCKDH kinase (BCKDK-cKO), which promotes BCAA catabolism by constitutively activating BCKDH activity in adult cardiomyocytes. Functional and molecular characterizations showed E1α inactivation in cardiomyocytes was sufficient to induce loss of cardiac function, systolic chamber dilation and pathological transcriptome reprogramming. On the other hand, inactivation of BCKDK in intact heart does not have an impact on baseline cardiac function or cardiac dysfunction under pressure overload. Our results for the first time established the cardiomyocyte cell autonomous role of BCAA catabolism in cardiac physiology. These mouse lines will serve as valuable model systems to investigate the underlying mechanisms of BCAA catabolic defect induced heart failure and to provide potential insights for BCAA targeted therapy.
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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.