Effect of compound EXP-2528 on angiotensin II-induced E-selectin and VCAM-1 expression in rat brain microvascular endothelial cells in vitro.
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 x 10(-7) mol x 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.
Liu
Hui-Qing
HQ
School of Medicine, Shandong University, Jinan 250012, China.
Wei
Xin-Bing
XB
Lou
Hai-Yan
HY
Zhang
Bin
B
Sun
Ru
R
Zhang
Xiu-Mei
XM
D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000098:blood supply; D002478:Cells, Cultured; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D007555:Isoxazoles / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology; D055806:Microvessels / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
C541959:2-butyl-4-chloro-5-formyl-1-((3-(2-methoxyphenyl)isoxazolyl-5-methyl))imidazole; D047228:Angiotensin II Type 1 Receptor Blockers; D019040:E-Selectin; D007093:Imidazoles; D007555:Isoxazoles; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II; D019808:Losartan