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Molecular Changes in Fatty Acid Oxidation in the Failing Heart

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Molecular Defects in Cardiovascular Disease

Abstract

Heart failure is emerging as a leading cause of morbidity and mortality in developed countries and is accompanied by alterations in myocardial fatty acid metabolism. In contrast to the normal heart, where fatty acid and glucose metabolism are reciprocally regulated, this dynamic relationship is perturbed in the failing heart. These metabolic alterations negatively impact both cardiac efficiency and function. Depending on the severity/stage of heart failure, the contribution of overall myocardial oxidative metabolism (fatty acid β-oxidation and glucose oxidation) to adenosine triphosphate (ATP) production can be depressed. Nonetheless, the balance between fatty acid β-oxidation and glucose oxidation is amenable to pharmacological intervention at multiple levels of each metabolic pathway. The alterations in fatty acid β-oxidation and the associated metabolic phenotype of accompany heart failure are described here. Furthermore, as myocardial fatty acid β-oxidation has emerged as a novel therapeutic target to limit the decrements in ventricular function, the rationale for the use of pharmacological agents that optimize fatty acid β-oxidation to improve cardiac function in the setting of heart failure will be described.

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Acknowledgments

This work was supported by a grant from the Canadian Institutes of Health Research to G.D.L. G.D.L. is an Alberta Heritage Foundation for Medical Research (AHFMR) Scientist. W.K. is supported by fellowship awards from the Heart and Stroke Foundation of Canada and AHFMR. W.W. is supported by a fellowship award from AHFMR. J.R.U. is supported by fellowship awards from AHFMR and the Canadian Institutes of Health Research.

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Authors and Affiliations

  1. Departments of Pediatrics and Pharmacology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada

    Jagdip S. Jaswal, Wendy Keung, Wei Wang & John R. Ussher

  2. Departments of Pediatrics and Pharmacology, University of Alberta, Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada

    Gary D. Lopaschuk

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  1. Jagdip S. Jaswal
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  2. Wendy Keung
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  3. Wei Wang
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  5. Gary D. Lopaschuk
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Correspondence to Gary D. Lopaschuk .

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  1. St. Boniface General Hospital, Research Centre, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

  2. Jikei University School of Medicine, Shibuya-ku, Ebisu 3-31-6, Tokyo, 150-0013, Japan

    Makoto Nagano

  3. Czech Republic, Institute of Physiology, Academy of Sciences of the, Videnska 1083, Prague, 142 20, Czech Republic

    Bohuslav Ostadal

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Jaswal, J.S., Keung, W., Wang, W., Ussher, J.R., Lopaschuk, G.D. (2011). Molecular Changes in Fatty Acid Oxidation in the Failing Heart. In: Dhalla, N., Nagano, M., Ostadal, B. (eds) Molecular Defects in Cardiovascular Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7130-2_12

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