© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Metabolic remodelling of the failing heart: the cardiac burn-out syndrome?
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands
* Corresponding author. Tel.: +31-43-3881204; fax: +31-43-3884166. marc.vanbilsen{at}fys.unimaas.nl
It has been postulated that the failing heart suffers from chronic energy starvation, and that derangements in cardiac energy conversion are accessory to the progressive nature of this disease. The molecular mechanisms driving this ‘metabolic remodelling’ process and their significance for the development of cardiac failure are still open to discussion. Next to changes in mitochondrial function, the hypertrophied heart is characterized by a marked shift in substrate preference away from fatty acids towards glucose. It has been argued that the decline in fatty acid oxidation is not fully compensated for by a rise in glucose oxidation, thereby imposing an additional burden on overall ATP generating capacity. Several lines of evidence suggest that these metabolic adaptations are brought about, at least in part, by alterations in the rate of transcription of genes encoding for proteins involved in substrate transport and metabolism. Here, the principal metabolic changes are reviewed and the various molecular mechanisms that are likely to play a role are discussed. In addition, the potential significance of these changes for the aetiology of heart failure is evaluated.
KEYWORDS Hypertrophy; Cardiac failure; Metabolism; High-energy phosphates; Mitochondria; Hypoxia-inducible factor; Peroxisome proliferator-activated receptor
Time for primary review 18 days
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