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Branched-Chain Amino Acid Metabolism in the Failing Heart

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Abstract

Branched-chain amino acids (BCAAs) are essential amino acids which have critical roles in protein synthesis and energy metabolism in the body. In the heart, there is a strong correlation between impaired BCAA oxidation and contractile dysfunction in heart failure. Plasma and myocardial levels of BCAA and their metabolites, namely branched-chain keto acids (BCKAs), are also linked to cardiac insulin resistance and worsening adverse remodelling in the failing heart. This review discusses the regulation of BCAA metabolism in the heart and the impact of depressed cardiac BCAA oxidation on cardiac energy metabolism, function, and structure in heart failure. While impaired BCAA oxidation in the failing heart causes the accumulation of BCAA and BCKA in the myocardium, recent evidence suggested that the BCAAs and BCKAs have divergent effects on the insulin signalling pathway and the mammalian target of the rapamycin (mTOR) signalling pathway. Dietary and pharmacological interventions that enhance cardiac BCAA oxidation and limit the accumulation of cardiac BCAAs and BCKAs have been shown to have cardioprotective effects in the setting of ischemic heart disease and heart failure. Thus, targeting cardiac BCAA oxidation may be a promising therapeutic approach for heart failure.

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Funding

GDL is funded by a Canadian Institute for Health Research Foundation Grant and a Heart and Stroke Foundation of Canada Grants. QGK is supported by an Alberta Innovates Postgraduate Fellowship in Health Innovation.

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  1. Cardiovascular Research Centre, University of Alberta, Edmonton, AB, T6G 2S2, Canada

    Qutuba G. Karwi & Gary D. Lopaschuk

  2. Department of Pharmacology, College of Medicine, University of Diyala, Diyala, Iraq

    Qutuba G. Karwi

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  1. Qutuba G. Karwi
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QGK and GDL conducted the literature search, critically appraised the literature, and wrote the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Gary D. Lopaschuk.

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Karwi, Q.G., Lopaschuk, G.D. Branched-Chain Amino Acid Metabolism in the Failing Heart. Cardiovasc Drugs Ther 37, 413–420 (2023). https://doi.org/10.1007/s10557-022-07320-4

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