Peroxisome Proliferator-Activated Receptor (PPAR)-α: A Pharmacological Target with a Promising Future
- Cite this article as:
- van Raalte, D.H., Li, M., Pritchard, P.H. et al. Pharm Res (2004) 21: 1531. doi:10.1023/B:PHAM.0000041444.06122.8d
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Peroxisome proliferator-activated receptor (PPAR)-α is a ligand-activated transcriptional factor that belongs to the family of nuclear receptors. PPAR-α regulates the expression of genes involved in fatty acid β-oxidation and is a major regulator of energy homeostasis. Fibrates are PPAR-α agonists and have been used to treat dyslipidemia for several decades because of their triglyceride (TG) lowering and high- density lipoprotein cholesterol (HDL-C) elevating effects. More recent research has demonstrated anti-inflammatory and anti-thrombotic actions of PPAR-α agonists in the vessel wall as well. Thus, PPAR-α agonists decrease the progression of atherosclerosis by modulating metabolic risk factors and by their anti-inflammatory actions on the level of the vascular wall. This is confirmed by several clinical studies, in which fibrates have shown to reduce atherosclerotic plaque formation and the event rate of coronary heart disease (CHD), especially in patients suffering from metabolic syndrome (MS). MS is characterized by a group of metabolic risk factors that include obesity, raised blood pressure, dyslipidemia, insulin resistance or glucose intolerance, and a prothrombotic state, and its incidence in the Western world is rising to epidemic proportions. This review paper will focus on the functions of PPAR-α in fatty acid β-oxidation, lipid metabolism, and vascular inflammation. Furthermore, PPAR-α genetics, the clinical use of PPAR-α activators and their future perspective will be discussed.