Document Detail

Targeting fatty acid and carbohydrate oxidation - a novel therapeutic intervention in the ischemic and failing heart.
MedLine Citation:
PMID:  21256164     Owner:  NLM     Status:  Publisher    
Cardiac ischemia and its consequences including heart failure, which itself has emerged as the leading cause of morbidity and mortality in developed countries are accompanied by complex alterations in myocardial energy substrate metabolism. In contrast to the normal heart, where fatty acid and glucose metabolism are tightly regulated, the dynamic relationship between fatty acid β-oxidation and glucose oxidation is perturbed in the ischemic and ischemic-reperfused heart, as well as in the failing heart. These metabolic alterations negatively impact both cardiac efficiency and function. Specifically there is an increased reliance on glycolysis during ischemia and fatty acid β-oxidation during reperfusion following ischemia as sources of ATP production. Depending on the severity of heart failure, the contribution of overall myocardial oxidative metabolism (fatty acid β-oxidation and glucose oxidation) to ATP production can be depressed, while that of glycolysis can be increased. Nonetheless, the balance between fatty acid β-oxidation and glucose oxidation is amenable to pharmacological intervention at multiple levels of each metabolic pathway. This review will focus on the pathways of cardiac fatty acid and glucose metabolism, and the metabolic phenotypes of the ischemic and ischemic/reperfused heart, as well as the metabolic phenotype of the failing heart. Furthermore, as energy substrate metabolism has emerged as a novel therapeutic intervention in these cardiac pathologies, this review will describe the mechanistic bases and rationale for the use of pharmacological agents that modify energy substrate metabolism to improve cardiac function in the ischemic and failing heart.
Jagdip S Jaswal; Wendy Keung; Wei Wang; John R Ussher; Gary D Lopaschuk
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-19
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  -     ISSN:  0006-3002     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2010. Published by Elsevier B.V.
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