Abstract
Advanced glycation end product (AGE) and receptor (RAGE) axis play a central role in the pathogenesis of diabetic vascular complications. Since peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been reported to reduce RAGE gene expression and subsequently suppress the downstream signalings in human umbilical vein endothelial cells (HUVECs), we examined here whether telmisartan, a unique angiotensin II type 1 receptor blocker with PPAR-γ agonistic activity, could inhibit the AGE-induced up-regulation of plasminogen activator inhibitor-1 (PAI-1) mRNA levels in HUVECs by suppressing RAGE gene expression. Telmisartan completely blocked the AGE-induced RAGE gene up-regulation in HUVECs, which was partly prevented by GW9662, an inhibitor of PPAR-γ. Further, telmisartan was also found to inhibit up-regulation of mRNA levels for PAI-1 in AGE-exposed HUVECs, which was completely prevented by GW9662. These results suggest that telmisartan inhibits the AGE-induced PAI-1 gene induction in HUVECs by down-regulating RAGE expression via PPAR-γ activation. Our present study suggests that telmisartan works as an anti-thrombogenic agent against AGEs, which may play a protective role against vascular complications in diabetes.
Keywords: AGEs, RAGE, Telmisartan, PAI-1, PPAR-γ
Letters in Drug Design & Discovery
Title: Telmisartan Blocks Advanced Glycation End Product (AGE)-Induced Plasminogen Activator Inhibitor-1 (PAI-1) Gene Expression in Endothelial Cells via Activation of Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ )
Volume: 5 Issue: 8
Author(s): Takanori Matsui, Kazuo Nakamura, Masayoshi Takeuchi and Sho-ichi Yamagishi
Affiliation:
Keywords: AGEs, RAGE, Telmisartan, PAI-1, PPAR-γ
Abstract: Advanced glycation end product (AGE) and receptor (RAGE) axis play a central role in the pathogenesis of diabetic vascular complications. Since peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been reported to reduce RAGE gene expression and subsequently suppress the downstream signalings in human umbilical vein endothelial cells (HUVECs), we examined here whether telmisartan, a unique angiotensin II type 1 receptor blocker with PPAR-γ agonistic activity, could inhibit the AGE-induced up-regulation of plasminogen activator inhibitor-1 (PAI-1) mRNA levels in HUVECs by suppressing RAGE gene expression. Telmisartan completely blocked the AGE-induced RAGE gene up-regulation in HUVECs, which was partly prevented by GW9662, an inhibitor of PPAR-γ. Further, telmisartan was also found to inhibit up-regulation of mRNA levels for PAI-1 in AGE-exposed HUVECs, which was completely prevented by GW9662. These results suggest that telmisartan inhibits the AGE-induced PAI-1 gene induction in HUVECs by down-regulating RAGE expression via PPAR-γ activation. Our present study suggests that telmisartan works as an anti-thrombogenic agent against AGEs, which may play a protective role against vascular complications in diabetes.
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Matsui Takanori, Nakamura Kazuo, Takeuchi Masayoshi and Yamagishi Sho-ichi, Telmisartan Blocks Advanced Glycation End Product (AGE)-Induced Plasminogen Activator Inhibitor-1 (PAI-1) Gene Expression in Endothelial Cells via Activation of Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ ), Letters in Drug Design & Discovery 2008; 5 (8) . https://dx.doi.org/10.2174/157018008786898590
DOI https://dx.doi.org/10.2174/157018008786898590 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
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