title: Olmesartan blocks inflammatory reactions in endothelial cells evoked by advanced glycation end products by suppressing generation of reactive oxygen species.
abstract: OBJECTIVE
  We have previously shown that interaction between advanced glycation end products (AGEs) and their receptor (RAGE) evokes generation of reactive oxygen species (ROS) and subsequently vascular inflammation, thus being involved in the development of diabetic retinopathy. Since there is crosstalk between the AGE-RAGE axis and the renin-angiotensin system in the pathogenesis of early diabetic retinopathy, we investigated in this study whether olmesartan, an angiotensin II type 1 receptor blocker, inhibited the AGE-evoked inflammatory reactions in endothelial cells (ECs) by suppressing ROS generation.
  
  
  METHODS
  ROS generation was evaluated by dihydroethidium staining. Gene and protein expression were analyzed by reverse-transcription polymerase chain reaction and ELISA, respectively.
  
  
  RESULTS
  Olmesartan significantly inhibited the AGE-evoked ROS generation and reduced the expression levels of monocyte chemoattractant protein 1 in microvascular ECs. Olmesartan also suppressed intercellular-adhesion molecule 1 expression in, and subsequently blocked T-cell adhesion to, AGE-exposed ECs.
  
  
  CONCLUSIONS
  The present study demonstrates for the first time that olmesartan inhibits AGE-evoked inflammatory reactions in ECs by suppressing ROS generation. Blockade of the renin-angiotensin system by olmesartan may play a protective role against diabetic retinopathy by attenuating the deleterious effects of AGEs through its antioxidative properties.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. shoichi@med.kurume-u.ac.jp
authors.forename: Sho-ichi
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Seiji
authors.initials: S
authors.lastname: Ueda
authors.forename: Seiya
authors.initials: S
authors.lastname: Okuda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Imaizumi
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced* / Q000517:prevention & control*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D018932:Chemokine CCL2; D017127:Glycation End Products, Advanced; D007093:Imidazoles; D017382:Reactive Oxygen Species; D013777:Tetrazoles; C081628:advanced glycation end products-bovine serum albumin; D018799:Intercellular Adhesion Molecule-1; D012710:Serum Albumin, Bovine; C437965:olmesartan