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-? (PPAR-?)

AUTHOR(S)
Matsui, Takanori; Nakamura, Kazuo; Takeuchi, Masayoshi; Yamagishi, Sho-ichi
PUB. DATE
November 2008
SOURCE
Letters in Drug Design & Discovery;Nov2008, Vol. 5 Issue 8, p477
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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-? (PPAR-?) 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-? 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-?. 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-? 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.
ACCESSION #
36303271

 

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