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Enhancing the metabolic substrate: PPAR-alpha agonists in heart failure.
MedLine Citation:
PMID:  21104312     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The prognosis for patients diagnosed with heart failure has significantly improved over the past three decades; however, the disease still confers a high degree of morbidity and mortality. Current treatments for chronic heart failure have focused primarily on blocking neurohormonal signaling and optimizing hemodynamic parameters. Although significant resources have been devoted toward the development of new pharmaceutical therapies for heart failure, few new drugs have been designed to target myocardial metabolic pathways despite growing evidence that on a fundamental level chronic heart failure can be characterized as an imbalance between myocardial energy demand and supply. Disruptions in myocardial energy pathways are evident as the myocardium is unable to generate sufficient amounts of ATP with advancing stages of heart failure. Down-regulation of fatty acid oxidation likely contributes to the phenotype of the "energy starved" heart. Fibrates are small molecule agonists of PPARα pathways that have been used to treat dyslipidemia. Although never used therapeutically in clinical heart failure, PPARα agonists have been shown to enhance fatty acid oxidation, improve endothelial cell function, and decrease myocardial fibrosis and hypertrophy in animal models of heart failure. In light of their excellent clinical safety profile, PPARα agonists may improve outcomes in patients suffering from systolic heart failure by augmenting myocardial ATP production in addition to targeting maladaptive hypertrophic pathways.
Authors:
Satyam Sarma; Hossein Ardehali; Mihai Gheorghiade
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Heart failure reviews     Volume:  17     ISSN:  1573-7322     ISO Abbreviation:  Heart Fail Rev     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9612481     Medline TA:  Heart Fail Rev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  35-43     Citation Subset:  IM    
Affiliation:
Division of Cardiology, Department of Medicine, Northwestern Memorial Hospital, Northwestern University, 251 East Huron, Chicago, IL, 60611, USA, s-sarma@md.northwestern.edu.
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