Targeting myocardial substrate metabolism in heart failure: potential for new therapies
Open Access
- 18 February 2012
- journal article
- review article
- Published by Wiley in European Journal of Heart Failure
- Vol. 14 (2), 120-129
- https://doi.org/10.1093/eurjhf/hfr173
Abstract
The incidence and prevalence of heart failure have increased significantly over the past few decades. Available data suggest that patients with heart failure independent of the aetiology have viable but dysfunctional myocardium that is potentially salvageable. Although a great deal of research effort has focused on characterizing the molecular basis of heart failure, cardiac metabolism in this disorder remains an understudied discipline. It is known that many aspects of cardiomyocyte energetics are altered in heart failure. These include a shift from fatty acid to glucose as a preferred substrate and a decline in the levels of ATP. Despite these demonstrated changes, there are currently no approved drugs that target metabolic enzymes or proteins in heart failure. This is partly due to our limited knowledge of the mechanisms and pathways that regulate cardiac metabolism. Better characterization of these pathways may potentially lead to new therapies for heart failure. Targeting myocardial energetics in the viable and potentially salvageable tissue may be particularly effective in the treatment of heart failure. Here, we will review metabolic changes that occur in fatty acid and glucose metabolism and AMP‐activated kinase in heart failure. We propose that cardiac energetics should be considered as a potential target for therapy in heart failure and more research should be done in this area.This publication has 101 references indexed in Scilit:
- Metformin Activates AMP Kinase through Inhibition of AMP DeaminaseOnline Journal of Public Health Informatics, 2011
- High‐energy phosphotransfer in the failing mouse heart: role of adenylate kinase and glycolytic enzymesEuropean Journal of Heart Failure, 2010
- Differential Cardiac Remodeling in Preload Versus AfterloadCirculation, 2010
- Glucagon-Like Peptide-1 Increases Myocardial Glucose Uptake via p38α MAP Kinase–Mediated, Nitric Oxide–Dependent Mechanisms in Conscious Dogs With Dilated CardiomyopathyCirculation: Heart Failure, 2010
- Progressive loss of creatine maintains a near normal ΔG∼ATP in transgenic mouse hearts with cardiomyopathy caused by overexpressing GsαJournal of Molecular and Cellular Cardiology, 2010
- AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic diseaseClinical Science, 2009
- Activation of AMP-Activated Protein Kinase by Metformin Improves Left Ventricular Function and Survival in Heart FailureCirculation Research, 2009
- Energy metabolism in heart failure and remodellingCardiovascular Research, 2008
- Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazineHeart, 2006
- AMPK alterations in cardiac physiology and pathology: enemy or ally?Journal Of Physiology-London, 2006