Olmesartan blocks inflammatory reactions in endothelial cells evoked by advanced glycation end products by suppressing generation of reactive oxygen species.
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.
Yamagishi
Sho-ichi
S
Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. shoichi@med.kurume-u.ac.jp
Matsui
Takanori
T
Nakamura
Kazuo
K
Inoue
Hiroyoshi
H
Takeuchi
Masayoshi
M
Ueda
Seiji
S
Okuda
Seiya
S
Imaizumi
Tsutomu
T
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*
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