title: Bazedoxifene blocks AGEs-RAGE-induced superoxide generation and MCP-1 level in endothelial cells.
abstract: Advanced glycation endproducts (AGEs) and their receptor (RAGE) play a role in vascular complications in diabetes. We have previously shown that 17β-estradiol at 10 nmol/l, a nearly identical plasma concentration to that during mid-pregnancy, up-regulates RAGE expression in endothelial cells. The finding might suggest the involvement of 17β-estradiol in the deterioration of vascular complications in diabetes during pregnancy. However, the effects of the selective estrogen receptor modulator, bazedoxifene, on oxidative and inflammatory reactions in AGEs-exposed endothelial cells remain unknown. In this study, we addressed the issue. Ten nmol/l 17β-estradiol increased RAGE and monocyte chemoattractant protein-1 (MCP-1) gene and protein expression in human umbilical vein endothelial cells (HUVECs), both of which were blocked by 10 nmol/l bazedoxifene. Bazedoxifene at 10 nmol/l also significantly inhibited the AGEs-induced superoxide generation, RAGE and MCP-1 gene and protein expression in HUVECs. The present study suggests that blockade of the AGEs-RAGE axis by bazedoxifene might be a novel therapeutic target for preventing vascular damage in diabetes, especially in postmenopausal women.
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications.
authors.forename: Y
authors.initials: Y
authors.lastname: Ishibashi
authors.forename: T
authors.initials: T
authors.lastname: Matsui
authors.forename: S
authors.initials: S
authors.lastname: Ueda
authors.forename: K
authors.initials: K
authors.lastname: Fukami
authors.forename: S
authors.initials: S
authors.lastname: Okuda
authors.forename: H
authors.initials: H
authors.lastname: Ohta
authors.forename: S
authors.initials: S
authors.lastname: Yamagishi
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage*; D013481:Superoxides / Q000737:chemistry*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D007211:Indoles; D000067759:Receptor for Advanced Glycation End Products; D020845:Selective Estrogen Receptor Modulators; D013481:Superoxides; C447119:bazedoxifene
keywords: AGEs; BAZEDOXIFENE; CARDIOVASCULAR DISEASE; OXIDATIVE STRESS; RAGE; SERM