title: [New concepts on the mechanism of action of fibrates and therapeutic prospectives in atherosclerosis].
abstract: Peroxisome Proliferator-Activated Receptors (PPARs) have been discovered 10 years ago as being orphan nuclear receptors. Three subtypes of PPAR(s) have been identified (alpha, gamma, delta). Activated PPARs bind to Peroxisome Proliferator Response Element which are localized in numerous gene promoters. PPAR(s) are activated by fatty acids and eicosanoids. PPAR-alpha activators (fibrates) improve plasma lipid levels and decrease CHD risk in patients with low HDL-cholesterol (gemfibrozil). They also decrease atherogenesis (fenofibrate) in patients with type 2 diabetes. These drugs decrease atherogenic lipoprotein plasma levels such as VLDL and small dense LDL and they increase anti-atherogenic HDL, through increases in apo A-I and apo A-II synthesis. Furthermore, they induce overexpression in HDL receptors, such as SR-BI/CLA-1 and ABCA1 which are capable to increase cellular cholesterol efflux. Therefore, fibrates would reduce atherogenesis through their capacity to increase the "reverse cholesterol transport". Moreover, they would reduce vascular inflammation by repressing NF-kappa B and AP-I transcriptional activity and they would reduce thrombosis risk by inhibiting tissue factor and fibrinogen synthesis.
authors.affiliation: Unité de Recherche sur les Lipoprotéines et l'Athérosclérose, Unité INSERM 545-Institut Pasteur et Université de Lille 2-1, rue du Professeur Calmette-59019 Lille.
authors.forename: J C
authors.initials: JC
authors.lastname: Fruchart
authors.forename: B
authors.initials: B
authors.lastname: Staels
authors.forename: P
authors.initials: P
authors.lastname: Duriez
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006801:Humans; D009765:Obesity / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000502:physiology*; D014157:Transcription Factors / Q000187:drug effects* / Q000502:physiology*
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors