Enhancing the metabolic substrate: PPAR-alpha agonists in heart failure

Satyam Sarma, Hossein Ardehali, Mihai Gheorghiade

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)35-43
Number of pages9
JournalHeart Failure Reviews
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

PPAR alpha
Heart Failure
Peroxisome Proliferator-Activated Receptors
Fatty Acids
Adenosine Triphosphate
Systolic Heart Failure
Fibric Acids
Dyslipidemias
Metabolic Networks and Pathways
Pharmaceutical Preparations
Hypertrophy
Myocardium
Fibrosis
Down-Regulation
Endothelial Cells
Animal Models
Hemodynamics
Morbidity
Phenotype
Safety

Keywords

  • Fatty acid metabolism
  • Glucose metabolism
  • Heart failure
  • Myocardial metabolism
  • PPAR alpha

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Enhancing the metabolic substrate : PPAR-alpha agonists in heart failure. / Sarma, Satyam; Ardehali, Hossein; Gheorghiade, Mihai.

In: Heart Failure Reviews, Vol. 17, No. 1, 01.01.2012, p. 35-43.

Research output: Contribution to journalArticle

Sarma, Satyam ; Ardehali, Hossein ; Gheorghiade, Mihai. / Enhancing the metabolic substrate : PPAR-alpha agonists in heart failure. In: Heart Failure Reviews. 2012 ; Vol. 17, No. 1. pp. 35-43.
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