The Effect of Dehydroepiandrosterone on the Expression of AT1 receptor and TNF-induced ICAM-1 in Vascular Smooth Muscle Cells

2005 
Objectives To further investigate the molecular mechanism of vasoprotective role of dehydroepiandrosterone (DHEA), we examined DHEA on AT1 receptor and ICAM-1 gene expression in vascular smooth muscle cells (VSMCs). Methods RT-PCR and Western Blot was used to determine the change of the expressions of mRNA and protein of AT1 and ICAM-1 when given various concentration dehydroepiandrosterone. Results 1.AT1 was abundant under the basal condition. The expression of AT1 mRNA and protein decreased after stimulated by DHEA (at 10^-10mol/L, 10^-8mol/L, 10^-6mol/L), and the effects of DHEA on AT1 protein was dose-dependent. ER inhibitor Tamoxifen and AR inhibitor Flutamide enhanced AT1 protein expression, but did not influence the mRNA expression. 2. The exp-ression of ICAM-1 gene was low under the basal condition.It increased when induced by TNF-α, but decreased when induced by DHEA (at 10^-10mol/L, 10^-8moL/L, 10^-6mol/L) ,and the effects of DHEA on ICAM-1 gene expression were dose-dependent. Conclusions These findings suggest that DHEA modulates AT1 and inflammatory factor induced ICAM-1 gene expression in VSMC, butfurther studies are necessary in the mecha-nism of DHEA action.
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