Effect of compound EXP-2528 on angiotensin Ⅱ-induced E-selectin and VCAM-1 expression in rat brain microvascular endothelial cells in vitro
- VernacularTitle:化合物EXP-2528对Ang Ⅱ诱导大鼠脑微血管内皮细胞表达E-selectin和VCAM-1的影响
- Author:
Huiqing LIU
;
Xinbing WEI
;
Haiyan LOU
;
Bin ZHANG
;
Ru SUN
;
Xiumei ZHANG
- Publication Type:Journal Article
- Keywords:
brain;
endothelial cell;
angiotensin II;
antagonist;
E-selectin;
vascular cell adhesion molecule-1
- From:
Acta Pharmaceutica Sinica
2007;42(8):822-827
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study is to investigate the effect and mechanism of angiotensin (Ang) II on E-selectin and vascular cell adhesion molecule-1 (VCAM-1) expression in rat brain microvascular endothelial cells (BMEC) and evaluate the effect of compound EXP-2528, a novel Ang Ⅱ type 1 (AT1) receptor antagonist. The experiment was performed in cultured BMEC of rat. The mRNA and protein expression of E-selectin and VCAM-1 in BMEC was analyzed by RT-PCR and Western blotting, respectively. The results showed that the mRNA and protein expression of E-selectin and VCAM-1 in BMEC were significantly upregulated by 4 h or 18 h exposure to 1×10-7 mol·L-1 Ang Ⅱ. These effects were abolished by pretreatment with the selective AT1 receptor antagonists losartan and compound EXP-2528, but not with the AT2 selective antagonist PD123319. Combining losartan with PD123319 also significantly inhibited Ang Ⅱ-induced E-selectin and VCAM-1 expression in BMEC, but there was no significant difference compared with losartan group. These findings indicated that Ang Ⅱ upregulated E-selectin and VCAM-1 in BMEC by activating AT1 receptor and then involved in the development of cerebrovascular disease.
