TY - JOUR
T1 - Telmisartan inhibits advanced glycation end products (AGEs)-elicited endothelial cell injury by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-γ activation
AU - Yamagishi, Sho Ichi
AU - Matsui, Takanori
AU - Nakamura, Kazuo
AU - Takeuchi, Masayoshi
AU - Inoue, Hiroyoshi
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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.
KW - AGEs
KW - PPAR-γ
KW - RAGE
KW - Renin-angiotensin system
KW - Telmisartan
UR - http://www.scopus.com/inward/record.url?scp=51449089179&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=51449089179&partnerID=8YFLogxK
U2 - 10.2174/092986608785203746
DO - 10.2174/092986608785203746
M3 - Article
C2 - 18855759
AN - SCOPUS:51449089179
SN - 0929-8665
VL - 15
SP - 850
EP - 853
JO - Protein and Peptide Letters
JF - Protein and Peptide Letters
IS - 8
ER -
