PPAR transcriptional activator complex polymorphisms and the promise of individualized therapy for heart failure

Neville F. Mistry, Sharon Cresci

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations

Abstract

The PPAR gene pathway consists of interrelated genes that encode transcription factors, enzymes, and downstream targets which coordinately act to regulate cellular processes central to glucose and lipid metabolism. The pathway includes the PPAR genes themselves, other class II nuclear hormone receptor transcription factors within the PPAR family, PPAR co-activators, PPAR co-repressors, and downstream metabolic gene targets. This review focuses on the transcription factors that comprise the PPAR transcriptional activator complex - the PPARs (PPARα, PPARβ, or PPARγ), PPAR heterodimeric partners, such as RXRα, and PPAR co-activators, such as PPARγ coactivator 1α (PGC-1α) and the estrogen-related receptors (ERRα, ERRβ, and ERRγ). These transcription factors have been implicated in the development of myocardial hypertrophy and dilated cardiomyopathy as well as response to myocardial ischemia/infarction and, by association, ischemic cardiomyopathy. Human expression studies and animal data are presented as the background for a discussion of the emerging field of pharmacogenetics as it applies to these genes and the consequent implications for the individualization of therapy for patients with heart failure.

Original languageEnglish
Pages (from-to)197-207
Number of pages11
JournalHeart Failure Reviews
Volume15
Issue number3
DOIs
StatePublished - May 2010

Keywords

  • Cardiovascular disease
  • ERR
  • PGC-1
  • PPAR
  • Peroxisome proliferator-activated receptor
  • Pharmacogenetics

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