Olmesartan blocks advanced glycation end products (AGEs)-induced angiogenesis in vitro by suppressing receptor for AGEs (RAGE) expression

Sho ichi Yamagishi, Takanori Matsui, Kazuo Nakamura, Hiroyoshi Inoue, Masayoshi Takeuchi, Seiji Ueda, Kei Fukami, Seiya Okuda, Tsutomu Imaizumi

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

We have previously shown that advanced glycation end products (AGEs)-their receptor (RAGE) interaction elicits angiogenesis through autocrine production of vascular endothelial growth factor (VEGF), thus suggesting the active involvement of the AGEs-RAGE system in proliferative diabetic retinopathy (PDR). Since the crosstalk between the AGEs-RAGE and the renin-angiotensin system has also been proposed in the pathogenesis of PDR, we investigated here whether olmesartan, an angiotensin II type 1 receptor blocker, inhibited the AGEs-elicited angiogenesis in vitro by suppressing the NF-κB-mediated RAGE expression. Olmesartan significantly inhibited the AGEs-induced NF-κB promoter activity and RAGE gene expression in cultured microvascular endothelial cells (ECs). Further, olmesartan was found to block the AGEs-induced up-regulation of VEGF mRNA levels and consequent increase in DNA synthesis in ECs. These results demonstrated for the first time that olmesartan inhibited the AGEs signaling to angiogenesis by suppressing RAGE expression in ECs. Our present study suggests that blockade of the renin-angiotensin system by olmesartan may play a protective role against PDR by attenuating the deleterious effects of AGEs via down-regulation of RAGE.

Original languageEnglish
Pages (from-to)130-134
Number of pages5
JournalMicrovascular Research
Volume75
Issue number1
DOIs
Publication statusPublished - 2008 Jan
Externally publishedYes

Fingerprint

Advanced Glycosylation End Products
Diabetic Retinopathy
Endothelial cells
Endothelial Cells
Renin-Angiotensin System
Angiotensins
Vascular Endothelial Growth Factor A
Renin
Angiotensin II Type 1 Receptor Blockers
olmesartan
Advanced Glycosylation End Product-Specific Receptor
In Vitro Techniques
Crosstalk
Gene expression
Up-Regulation
Down-Regulation
Gene Expression
Messenger RNA
DNA

Keywords

  • AGEs
  • Angiogenesis
  • Diabetic retinopathy
  • RAGE
  • VEGF

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine

Cite this

Olmesartan blocks advanced glycation end products (AGEs)-induced angiogenesis in vitro by suppressing receptor for AGEs (RAGE) expression. / Yamagishi, Sho ichi; Matsui, Takanori; Nakamura, Kazuo; Inoue, Hiroyoshi; Takeuchi, Masayoshi; Ueda, Seiji; Fukami, Kei; Okuda, Seiya; Imaizumi, Tsutomu.

In: Microvascular Research, Vol. 75, No. 1, 01.2008, p. 130-134.

Research output: Contribution to journalArticle

Yamagishi, Sho ichi ; Matsui, Takanori ; Nakamura, Kazuo ; Inoue, Hiroyoshi ; Takeuchi, Masayoshi ; Ueda, Seiji ; Fukami, Kei ; Okuda, Seiya ; Imaizumi, Tsutomu. / Olmesartan blocks advanced glycation end products (AGEs)-induced angiogenesis in vitro by suppressing receptor for AGEs (RAGE) expression. In: Microvascular Research. 2008 ; Vol. 75, No. 1. pp. 130-134.
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