Peroxisome proliferator-activated receptors: are they involved in atherosclerosis progression?

Peroxisome proliferator-activated receptors (PPAR) are nuclear receptors present in several organs and cell types. They are subdivided into PPAR alpha, PPAR gamma and PPAR delta (or beta). PPAR alpha and gamma are the two main categories of these receptors, which are both characterized by their ability to influence lipid metabolism, glucose homeostasis, cell proliferation, differentiation and apoptosis, as well as the inflammatory response, by transcriptional activation of target genes. PPAR alpha are activated by fatty acids, eicosanoids and fibrates, while PPAR gamma activators include arachidonic acid metabolites, oxidized low density lipoprotein and thiazolidinediones. Atherosclerosis is now considered a chronic inflammatory condition. Thus, PPAR activation appears a promising approach to favorably affect atherosclerosis development through both metabolic and anti-inflammatory effects. However, the clinical data in favor of an anti-atherosclerotic action of PPAR agonists are still scanty, and some experimental data would even indicate possible pro-atherogenic effects, or a lack of effect in the female sex. New controlled clinical studies will provide the information necessary to understand the true significance and usefulness of PPAR alpha, gamma and delta activators in the control of atherosclerotic disease.