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

• Published in: Atherosclerosis Vol. 125; no. 1; pp. 27 - 38
• Main Authors: Akishita, Masahiro, Ouchi, Yasuyoshi, Miyoshi, Hideyuki, Orimo, Akira, Kozaki, Koichi, Eto, Masato, Ishikawa, Michiro, Kim, Seungbum, Toba, Kenji, Orimo, Hajime
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 23.08.1996; Elsevier
• Subjects: Animals; Aorta - metabolism; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; c- fos; Cardiology. Vascular system; DNA - biosynthesis; Endothelin; Endothelin-1 - metabolism; Estradiol - analogs & derivatives; Estradiol - pharmacology; Estrogen; Estrogens - pharmacology; Female; Femoral Artery - drug effects; Femoral Artery - metabolism; Gene Expression Regulation; Immunohistochemistry; Medical sciences; Ovariectomy; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Wistar; RNA, Messenger - analysis; Smooth muscle cell; Smooth muscle cell; Endothelin; c- fos; Estrogen; Atherosclerosis; Femoral artery; Rat; Rodentia; Cardiovascular disease; Smooth muscle; Endothelin 1; Gene expression; Vascular disease; Vertebrata; Mammalia; Messenger RNA; Gene; Blood vessel; Animal; DNA; Aorta; Circulatory system; Inhibition; Sex steroid hormone
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/0021-9150(96)05836-4

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- fos 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.