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Peroxisome Proliferator-Activated Receptor Ligands as Antiatherogenic Agents: Panacea or Another Pandora's Box?

Neda Rasouli, MD

Jawahar L. Mehta, MD, PhD

Division of Cardiovascular Medicine, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR.

Peroxisome proliferator activated receptors (PPARs) are members of the nuclear receptor super family that modulate gene expression upon ligand activation. They are 3 major subtypes of PPARs: alpha, delta (also called beta), and gamma. PPAR- is widely expressed in the cardiovascular system and is involved in the regulation of tissue inflammation and smooth muscle cell growth pathways as well as in lipoprotein metabolism and coagulation cascades. PPAR- ligands of (e.g., rosigitazone and pioglitazone) have been shown to exert antiatherogenic effects both in vitro and in vivo. PPAR- ligands (e.g., clofibrate and benzofibrate) modulate lipoprotein metabolism, and affect inflammation and coagulation cascade. These effects may be helpful in resolving the dilemma arising from studies that showed significant mortality and morbidity benefits of fibrates in the face of minimal changes in HDL-cholesterol levels. The role of PPAR- in atherogenesis remains largely unknown, although it appears that PPAR- activation affects lipoprotein metabolism. PPAR ligands appear to be promising agents in limiting atherosclerosis; however, large-scale clinical trials are required to assess their safety and efficacy before they can be added to the clinicians' arsenal of antiatherosclerotic agents.

Key Words: atherosclerosis • inflammation • peroxisome proliferator activated receptors

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