ArticleCirculation. Heart failure2015
Metabolic efficiency promotes protection from pressure overload in hearts expressing slow skeletal troponin I.
Article in Circulation. Heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- CPT1a Expression Is a Critical Cardioprotective Response to Pathological Stress That Enables Rescue by Gene Transfer.Circulation research · 2026Article
- Integrated proteomics identifies troponin I isoform switch as a regulator of a sarcomere-metabolism axis during cardiac regeneration.Cardiovascular research · 2025Article
- Cardiac troponin I directly binds and inhibits mitochondrial ATP synthase with a noncanonical role in the post-ischemic heart.Nature cardiovascular research · 2024Article
- A defect in mitochondrial protein translation influences mitonuclear communication in the heart.Nature communications · 2023Article
- The lack of Troponin I Ser-23/24 phosphorylation is detrimental to in vivo cardiac function and exacerbates cardiac disease.Journal of molecular and cellular cardiology · 2023Article
- The Hippo Signaling Pathway as a Drug Target in Familial Dilated Cardiomyopathy.International journal of drug discovery and pharmacology · 2022Article
- Calorie restriction changes lipidomic profiles and maintains mitochondrial function and redox balance during isoproterenol-induced cardiac hypertrophy.Journal of physiology and biochemistry · 2022Article
- Preservation of Acyl Coenzyme A Attenuates Pathological and Metabolic Cardiac Remodeling Through Selective Lipid Trafficking.Circulation · 2019Article
- Article
- A Similar Metabolic Profile Between the Failing Myocardium and Tumor Could Provide Alternative Therapeutic Targets in Chemotherapy-Induced Cardiotoxicity.Frontiers in cardiovascular medicine · 2018Article
- Multiphasic Regulation of Systemic and Peripheral Organ Metabolic Responses to Cardiac Hypertrophy.Circulation. Heart failure · 2017Article
- Peroxisome proliferator-activated receptor-α expression induces alterations in cardiac myofilaments in a pressure-overload model of hypertrophy.American journal of physiology. Heart and circulatory physiology · 2017Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe failing heart displays increased glycolytic flux that is not matched by a commensurate increase in glucose oxidation. This mismatch induces increased anaplerotic flux and inefficient glucose metabolism. We previously found adult transgenic mouse hearts expressing the fetal troponin I isoform, (ssTnI) to be protected from ischemia by increased glycolysis. In this study, we investigated the metabolic response of adult mouse hearts expressing ssTnI to chronic pressure overload. METHODS AND
resultsAt 2 to 3 months of age, ssTnI mice or their nontransgenic littermates underwent aortic constriction (TAC). TAC induced a 25% increase in nontransgenic heart size but only a 7% increase in ssTnI hearts (P<0.05). Nontransgenic TAC developed diastolic dysfunction (65% increase in E/A ratio), whereas the E/A ratio actually decreased in ssTnI TAC. Isolated perfused hearts from nontransgenic TAC mice showed reduced cardiac function and reduced creatine phosphate:ATP (16% reduction), but ssTnI TAC hearts maintained cardiac function and energy charge. Contrasting nontransgenic TAC, ssTnI TAC significantly increased glucose oxidation at the expense of palmitate oxidation, preventing the increase in anaplerosis observed in nontransgenic TAC hearts. Elevated glucose oxidation was mediated by a reduction in pyruvate dehydrogenase kinase 4 expression, enabling pyruvate dehydrogenase to compete against anaplerotic enzymes for pyruvate carboxylation.
conclusionsExpression of a single fetal myofilament protein into adulthood in the ssTnI-transgenic mouse heart induced downregulation of the gene expression response for pyruvate dehydrogenase kinase to pressure overload. The consequence of elevated pyruvate oxidation in ssTnI during TAC reduced anaplerotic flux, ameliorating inefficiencies in glucose oxidation, with energetic and functional protection against cardiac decompensation.
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