Telmisartan inhibits methylglyoxal-mediated cell death in human vascular endothelium.
Methylglyoxal (MGO) is a metabolite of glucose. Since serum MGO level is increased in diabetic patients, MGO is implicated in diabetic complications related to vascular injury. We have recently demonstrated that glucose metabolite is a more powerful stimulant for endothelial cells (ECs) injury rather than glucose or advanced glycation-end products. Recent clinical trials suggest that angiotensin receptor blockers are effective to prevent diabetes-associated cardiovascular disorders beyond blood pressure lowering effect. To explore the mechanisms, we examined effects of telmisartan on MGO-induced ECs injury. Treatment of human umbilical vein ECs with MGO (560 microM) induced time-dependent (0-24 h) cell death. MGO-induced cell death was apoptosis since MGO increased cleaved caspase-3 expression. Telmisartan (0.1-10 microM) inhibited MGO-induced cell death and caspase-3 activation. These results indicate that telmisartan prevents MGO-induced apoptosis by inhibiting caspase-3 activation, which might explain at least in part the beneficial effects of telimisartan against diabetes-related cardiovascular diseases.
Department of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada, Aomori 034-8628, Japan.
Tatsuya
T
Baden
Hideyuki
H
Yamawaki
Kazuaki
K
Saito
Masashi
M
Mukohda
Muneyoshi
M
Okada
Yukio
Y
Hara
D047228:Angiotensin II Type 1 Receptor Blockers; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D011765:Pyruvaldehyde / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000077333:Telmisartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D011765:Pyruvaldehyde; D053148:Caspase 3; D000077333:Telmisartan