PPARs in inflammation, atherosclerosis and thrombosis

PPARs are transcription factors which regulate lipid and lipoprotein metabo lism, glucose homeostasis and cellular differentiation. PPAR alpha enhances fatty acid oxidation whereas PPAR gamma promotes adipogenesis and fatty ac id storage in adipose tissue. Both PPAR alpha and PPAR gamma improve glucos e homeostasis. PPAR alpha and PPAR gamma are activated by the pharmacologic al agents fibrates and glitazones respectively, and by natural fatty acid d erivatives, including inflammation mediators. PPARs are expressed in the di fferent cell types of human atherosclerotic lesions where they regulate the expression of genes involved in the inflammatory response and lipid homeos tasis. PPARs modulate the recruitment and adhesion of leukocytes and monocy tes to the atherosclerotic lesion. PPARs furthermore control macrophage lip id homeostasis through their action on scavenger receptors and by regulatin g genes involved in the first steps of the reverse cholesterol transport pa thway. Finally, PPARs regulate genes controlling thrombogenicity associated with plaque rupture. These observations suggest that PPARs modulate athero sclerosis development by acting at both metabolic and vascular levels. This review will essentially focus on the functions of PPAR alpha and PPAR gamm a in immunoregulation, vascular inflammation and thrombosis associated to a therosclerosis. J Cardiovasc Risk 8:187-194 (C) 2001 Lippincott Williams & Wilkins.