title: Atorvastatin exerts its anti-atherosclerotic effects by targeting the receptor for advanced glycation end products.
abstract: Recent studies demonstrated the beneficial role of atorvastatin in reducing the risk of cardiovascular morbidity and mortality in patients with diabetes mellitus and/or metabolic syndrome. To investigate the mechanisms underlying the anti-atheroscleroic action of atorvastatin, we examined the expression of the receptor for advanced glycation end products (RAGE) and its downstream target gene, monocyte chemoattractant protein-1 (MCP-1) using real-time PCR. In in vitro studies, exposure to high glucose or AGE induced oxidative stress and activation of the AGE/RAGE system in human umbilical vein endothelial cells. Treatment of the cells with atorvastatin significantly released the oxidative stress by restoring the levels of glutathione and inhibited the RAGE upregulation. In diabetic Goto Kakisaki (GK) rats fed with a high-fat diet for 12weeks, RAGE and MCP-1 were upregulated in the aortas, and there was a significant correlation between RAGE and MCP-1 mRNA abundance (r=0.482, P=0.031). Treatment with atorvastatin (20mg/kg qd) significantly downregulated the expression of RAGE and MCP-1. These data thus demonstrate a novel "pleiotropic" activity of atorvastatin in reducing the risk of cardiovascular diseases by targeting RAGE expression.
authors.affiliation: Department of Endocrinology, The Affiliated East Hospital, Tongji University, Shanghai, PR China. fengbo@medmail.com.cn
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Yan
authors.forename: Junli
authors.initials: J
authors.lastname: Xue
authors.forename: Fengjing
authors.initials: F
authors.lastname: Liu
authors.forename: Ji-Fan
authors.initials: JF
authors.lastname: Hu
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic
chemical_list: D006538:Heptanoic Acids; D011758:Pyrroles; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000069059:Atorvastatin