Telmisartan inhibits advanced glycation end products (AGEs)-elicited endothelial cell injury by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-γ activation

Sho Ichi Yamagishi, Takanori Matsui, Kazuo Nakamura, Masayoshi Takeuchi, Hiroyoshi Inoue

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Advanced glycation end products (AGEs)-their receptor (RAGE) axis plays a central role in the pathogenesis of diabetic microangiopathy. Since the pathophysiological crosstalk between the AGEs-RAGE system and angiotensin II has also been associated with diabetic microangiopathy, we examined here whether and how telmisartan, a unique angiotensin II type 1 receptor blocker (ARB) with peroxisome proliferator-activated receptor-γ (PPAR-γ)-modulating activity, could inhibit the AGEs-elicited endothelial cell injury by suppressing RAGE expression in vitro. Telmisartan suppressed RAGE expression at both mRNA and protein levels in human cultured microvascular endothelial cells (ECs), which were prevented by GW9662, an inhibitor of PPAR-γ. Further, telmisartan was found to inhibit up-regulation of mRNA levels for monocyte chemoattractant protein-1, intercellular adhesion molecule-1 and vascular endothelial growth factor in AGEs-exposed ECs. These results suggest that telmisartan inhibits the AGEs-elicited EC injury by down-regulating RAGE expression via PPAR-γ activation. Our present study provides a unique beneficial aspect of telmisartan. Specifically, it could work as an anti-inflammatory agent against AGEs via PPAR-γ activation and may play a protective role against diabetic microangiopathy.

Original languageEnglish
Pages (from-to)850-853
Number of pages4
JournalProtein and Peptide Letters
Volume15
Issue number8
DOIs
Publication statusPublished - 2008 Aug
Externally publishedYes

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Peroxisome Proliferator-Activated Receptors
Advanced Glycosylation End Products
Endothelial cells
Endothelial Cells
Diabetic Angiopathies
Chemical activation
Wounds and Injuries
Angiotensin II Type 1 Receptor Blockers
Messenger RNA
Chemokine CCL2
Intercellular Adhesion Molecule-1
Crosstalk
Angiotensin II
Vascular Endothelial Growth Factor A
Anti-Inflammatory Agents
Up-Regulation
telmisartan
Advanced Glycosylation End Product-Specific Receptor
Proteins

Keywords

  • AGEs
  • PPAR-γ
  • RAGE
  • Renin-angiotensin system
  • Telmisartan

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Telmisartan inhibits advanced glycation end products (AGEs)-elicited endothelial cell injury by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-γ activation. / Yamagishi, Sho Ichi; Matsui, Takanori; Nakamura, Kazuo; Takeuchi, Masayoshi; Inoue, Hiroyoshi.

In: Protein and Peptide Letters, Vol. 15, No. 8, 08.2008, p. 850-853.

Research output: Contribution to journalArticle

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