Estrogen inhibits endothelin-1 production and c-fos gene expression in rat aorta

被引:50
作者
Akishita, M [1 ]
Ouchi, Y [1 ]
Miyoshi, H [1 ]
Orimo, A [1 ]
Kozaki, K [1 ]
Eto, M [1 ]
Ishikawa, M [1 ]
Kim, S [1 ]
Toba, K [1 ]
Orimo, H [1 ]
机构
[1] UNIV TOKYO,FAC MED,DEPT GERIATR,BUNKYO KU,TOKYO 113,JAPAN
关键词
estrogen; endothelin; c-fos; atherosclerosis; smooth muscle cell;
D O I
10.1016/0021-9150(96)05836-4
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In order to clarify the mechanism underlying the preventive effect of estrogen on atherogenesis, we investigated the role of estrogen in the regulation of endothelin-1 (ET-1) production and c-Sos mRNA expression, which may contribute to atherogenesis. Plasma ET-1 concentration in ovariectomized rats (OVX) was twice as high as that in sham-operated female rats (Sham). Estradiol replacement in OVX rats (OVX + E) decreased plasma ET-1 to the level in Sham (Sham, 0.68 +/- 0.14; OVX, 1.32 +/- 0.14; OVX + E, 0.85 +/- 0.12 pg/ml). Metabolic clearance rate of ET-1 was similar in these three groups of rats, suggesting that the difference in plasma ET-1 was due to production rather than degradation. Measurement of immunoreactive ET-1 in tissue extract and immunohistochemical examination showed that expression of ET-1 in the aortic smooth muscle cells of OVX was increased. The expression of c-fos mRNA in the aorta was also increased in OVX compared with Sham and OVX + E. Intravenous infusion of ET-1 to Sham induced c-fos expression in the aorta, suggesting the contribution of ET-1 to c-fos expression. Tissue culture study revealed that DNA synthesis was increased in the aorta and femoral artery of OVX. These results suggest that inhibition of ET-1 and c-fos expression is involved in the anti-atherogenic action of estrogen.
引用
收藏
页码:27 / 38
页数:12
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