Peroxisome proliferator-activated receptor-alpha and atherosclerosis: From basic mechanisms to clinical implications

Zarmen Israelian-Konaraki, Peter D. Reaven

Research output: Contribution to journalReview article

54 Scopus citations

Abstract

Atherosclerosis is an inflammatory process, triggered by the presence of lipids in the vascular wall, and encompasses a complex interaction among inflammatory cells, vascular elements, and lipoproteins through expression of several adhesion molecules and cytokines. Activation of the nuclear receptor, peroxisome proliferator-activated receptor-α (PPAR-α), has been demonstrated to modulate many aspects of lipoprotein metabolism and inflammation in vitro as well as in animal and human studies. The tissue distribution of PPAR-α is extensive, and it is abundantly present in the vascular wall where it may mediate many of antiinflammatory and antiatherogenic effects. Major clinical trials such as the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT), the Helsinki Heart Study, and the Diabetes Atherosclerosis Intervention Study (DAIS) have demonstrated the beneficial effects of synthetic agonists of PPAR-α, specifically fibric acid derivatives, on cardiovascular disease outcome. Although fibric acid trials have reported cardiovascular risk reduction in patients with dyslipidemia, the favorable alterations in plasma lipids can only partially explain the reduction in cardiovascular events in these studies. One common link among these trials was a cohort with a high prevalence of insulin resistance or diabetes, conditions associated with heightened systemic inflammation and increased risk for development and progression of atherosclerosis. We review the many antiatherogenic effects of PPAR-α ligands and evidence from fibric acid trials that individuals with insulin resistance or diabetes benefit the most from these drugs, consistent with their antiinflammatory and antithrombotic properties.

Original languageEnglish (US)
Pages (from-to)240-246
Number of pages7
JournalCardiology in Review
Volume13
Issue number5
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

Keywords

  • Atherosclerosis
  • Cardiovascular disease
  • Fibric acids
  • Inflammation
  • PPAR-α

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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