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Different effects of telmisartan and valsartan on human aortic vascular smooth muscle cell proliferation

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Author:
No author available
Journal Title:
Chinese Medical Journal
Issue:
12
DOI:
10.3760/cma.j.issn.0366-6999.2012.12.021
Key Word:
telmisartan;angiotensin Ⅱ receptor;peroxisome proliferator-activated receptor,human aortic smooth muscle cell

Abstract: Background Vascular smooth muscle cell proliferation is an important process in the development of atherosclerosis and is associated with other cellular processes in atherogenesis.Telmisartan is reported to have partial peroxisome proliferator-activated receptor (PPAR)-Y activating properties and has been referred to as selective PPAR modulators,but valsartan just blocks angiotensin Ⅱ (Angll) type 1 (AT1) receptors.This study aimed to compare the different effects of telmisartan and valsartan on human aortic smooth muscle cells (HASMCs) proliferation.Methods Ability of telmisartan and valsartan to inhibit proliferation of HASMCs was evaluated by the Cell Counting Kit-8 (CCK-8) in continuous cell culture.Whether the antiproliferative effects of telmisartan and valsartan depend on their effects on Angll receptors or activating the peroxisome PPAR-Y was also investigated in this study.Results Telmisartan inhibited proliferation of HASMCs by 52.4% (P <0.01) at the concentration of 25 μmol/L and the effect depended on the dose of telmisartan,but valsartan had little effect on HASMCs proliferation (P >0.05) and no dose response.When tested in cells stimulated with Angll,telmisartan had the same inhibition of HASMCs by 59.2% (P <0.05) and valsartan also inhibited it by 41.6% (P <0.05).Telmisartan and valsartan had the same effect on down-regulating AT1 receptor expression and telmisartan was supedor to valsartan up-regulating Angll type 2 (AT2) receptor expression.Antiproliferative effects of telmisartan were observed when HASMCs were treated with the PPAR-y antagonist GW9662 but antiproliferative effects of the PPAR-Y activator pioglitazone were not observed.Conclusions Telmisartan,but not valsartan,inhibits HASMCs proliferation and has dose-dependent response without stimulation of Angll.AT2 receptor up-regulation of telmisartan contributes to its greater antiproliferative effects than valsartan.Its PPAR-Y activation does not play a cdtical role in inhibiting HASMCs proliferation.

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