Targeting mitochondrial oxidative metabolism as an approach to treat heart failure.

Abstract

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.

• Authors: Natasha Fillmore, Gary D Lopaschuk
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1833 Issue 4 Pg. 857-65 (Apr 2013) ISSN: 0006-3002 [Print] Netherlands
• PMID: 22960640 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Adrenergic beta-Antagonists
• Enzyme Inhibitors
• Fatty Acids
• Peroxisome Proliferator-Activated Receptors
• Pyruvate Dehydrogenase Acetyl-Transferring Kinase
• Receptors, Adrenergic, beta
• Protein Serine-Threonine Kinases
• Glucose

Topics

• Adrenergic beta-Antagonists (pharmacology, therapeutic use)
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Fatty Acids (antagonists & inhibitors, metabolism)
• Glucose (metabolism)
• Heart (drug effects, physiopathology)
• Heart Failure (drug therapy, metabolism, physiopathology)
• Humans
• Mitochondria (drug effects, metabolism)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Oxidative Phosphorylation (drug effects)
• Peroxisome Proliferator-Activated Receptors (agonists, genetics, metabolism)
• Protein Serine-Threonine Kinases (antagonists & inhibitors, genetics, metabolism)
• Pyruvate Dehydrogenase Acetyl-Transferring Kinase
• Receptors, Adrenergic, beta (genetics, metabolism)