Induction of cyclooxygenase-2 by angiotensin II in cultured rat vascular smooth muscle cells

被引:124
作者
Ohnaka, K [1 ]
Numaguchi, K [1 ]
Yamakawa, T [1 ]
Inagami, T [1 ]
机构
[1] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA
关键词
angiotensin II; cyclooxygenase; 2; protein kinases; muscle; smooth; vascular;
D O I
10.1161/01.HYP.35.1.68
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Angiotensin II (Ang II) stimulates the release of prostaglandins (PGs) in various cells and tissues. Recently, cyclooxygenase-2 (COX-2) emerged as a new key regulator for PG synthesis. In the present study, we investigated whether Ang II regulates COX-2 expression in cultured rat vascular smooth muscle cells (VSMCs). Ang II markedly increased the expression of COX-2 mRNA in a time- and dose-dependent manner. This effect was completely blocked by the Ang II type 1 receptor antagonist losartan but not by the Ang II type 2 receptor antagonist PD 123319. The p42/44 mitogen-activated protein kinase (MAPK) kinase-1 inhibitor PD98059 and the p38 MAPK inhibitor SB203580 significantly suppressed Ang II-induced COX-2 mRNA and protein expression. Ang II did not increase transcription of the COX-2 gene, as examined with a COX-2 promoter/luciferase chimeric plasmid construct. Instead, it suppressed the degradation of COX-2 mRNA. PD98059 and SB203580 markedly enhanced the decay of COX-2 mRNA induced by Ang II, implying that p42/44 and p38 MAPK activated by Ang II play a role in the regulation of COX-2 through stabilization of its mRNA. The COX-2-specific inhibitor NS-398 attenuated Ang II-stimulated DNA and protein synthesis, as well as PGE(2) production by VSMCs. These results suggest that Ang II regulates COX-2 expression and PG production and modulates cell proliferation through MAPK-mediated signaling pathways in rat VSMCs.
引用
收藏
页码:68 / 75
页数:8
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