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Olmesartan Blocks Inflammatory Reactions in Endothelial Cells Evoked by Advanced Glycation End Products by Suppressing Generation of Reactive Oxygen Species

Yamagishi S.a · Matsui T.a · Nakamura K.a · Inoue H.c · Takeuchi M.d · Ueda S.b · Okuda S.b · Imaizumi T.a
Divisions of aCardiovascular Medicine and bNephrology, Department of Medicine, and cRadioisotope Institute for Basic and Clinical Medicine, Kurume University School of Medicine, Kurume, and dDepartment of Pathophysiological Science, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa, Japan Ophthalmic Res 2008;40:10–15 (DOI:10.1159/000111152)

Abstract

Background/Aims: 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. Olme-sartan 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.

 

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