PPARα and Atherosclerosis

Over the past five years, several groups, including ours, began pursuing the hypothesis that peroxisome proliferator activated receptors (PPARs) might be expressed in the vasculature, directly influencing important vascular responses. Certainly such notions were well-based, given established roles for PPARs in regulating metabolic processes, such as lipids, glucose homeostasis, and adipogenesis, known to critically influence the vessel wall. Furthermore, the use of PPAR agonists, like thiazolidinediones and fibric acid derivatives in clinical situations with increased cardiovascular risk, like diabetes and dyslipidemia (high triglycerides/low HDL), underscored the potential involvement of PPARα in vascular biology and specifically atherosclerosis. Such issues are of particular relevance in regards to PPAR alpha (PPARα), given putative natural ligands such as certain fatty acids, and the existence of clinical trials utilizing PPARα ligands that focus on cardiovascular endpoints. In fact, our interest in PPARα grew out of prior observations from our group that certain fatty acids, like docosahexanoic acid (DHA), inhibit the induction of adhesion molecules like VCAM-1, although the mechanism for this response remained unclear [1].