Targeting mitochondrial oxidative metabolism as an approach to treat heart failure

• Published in: Biochimica et biophysica acta Vol. 1833; no. 4; pp. 857 - 865
• Main Authors: Fillmore, Natasha, Lopaschuk, Gary D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-04-2013
• Subjects: Adrenergic beta-Antagonists - pharmacology; Adrenergic beta-Antagonists - therapeutic use; Carnitine palmitoyltransferase 1; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Fatty acid oxidation; Fatty Acids - antagonists & inhibitors; Fatty Acids - metabolism; Glucose - metabolism; Glucose oxidation; Glycolysis; Heart - drug effects; Heart - physiopathology; Heart failure; Heart Failure - drug therapy; Heart Failure - metabolism; Heart Failure - physiopathology; Humans; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Oxidative Phosphorylation - drug effects; Peroxisome Proliferator-Activated Receptors - agonists; Peroxisome Proliferator-Activated Receptors - genetics; Peroxisome Proliferator-Activated Receptors - metabolism; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Receptors, Adrenergic, beta - genetics; Receptors, Adrenergic, beta - metabolism; Heart failure; Fatty acid oxidation; Glycolysis; Mitochondria; Glucose oxidation; Carnitine palmitoyltransferase 1
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2012.08.014

Heart failure is a major cause of morbidity and mortality in the world. Cardiac energy metabolism, specifically fatty acid and glucose metabolism, is altered in heart failure and has been implicated as a contributing factor in the impaired heart function observed in heart failure patients. There is emerging evidence demonstrating that correcting these changes in energy metabolism by modulating mitochondrial oxidative metabolism may be an effective treatment for heart failure. Promising strategies include the downregulation of fatty acid oxidation and an increased coupling of glycolysis to glucose oxidation. Carnitine palmitoyl transferase I (CPT1), fatty acid β-oxidation enzymes, and pyruvate dehydrogenase kinase (PDK) are examples of metabolic targets for the treatment of heart failure. While targeting mitochondrial oxidative metabolism is a promising strategy to treat heart failure, further studies are needed to confirm the potential beneficial effect of modulating these metabolic targets as an approach to treating heart failure. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.
► Significant alterations in energy metabolism occur in the failing heart. ► Cardiac mitochondrial oxidative metabolism decreases in heart failure. ► Glycolysis increases in the failing heart. ► Optimizing energy metabolism is a novel approach to treat heart failure. ► Inhibiting fatty acid oxidation and stimulating glucose oxidation improves cardiac efficiency and function in heart failure.