Estrogen actions and in situ synthesis in human vascular smooth muscle cells and their correlation with atherosclerosis

Yasuhiro Nakamura, Takashi Suzuki, Hironobu Sasano

研究成果: Article査読

25 被引用数 (Scopus)

抄録

Various epidemiological studies have demonstrated a relatively low incidence of cardiovascular events in premenopausal women and its marked increment after menopause. In addition, estrogens have been postulated to exert direct anti-atherogenic effects via binding to estrogen receptors (ERs) in vascular smooth muscle cells (VSMCs). However, not all postmenopausal women develop atherosclerosis despite decreased levels of serum estrogen. Therefore, it is considered important to examine the status of estrogen metabolism in situ and of ER expression in the human cardiovascular system. Estrone sulfate (E 1S) is a major circulating plasma estrogen that is converted into the biologically active estrogen, estrone (E1) by steroid sulfatase (STS). E1 is also sulfated and reverted into E1S by estrogen sulfotransferase (EST). These two enzymes have recently been shown to play important roles in the in situ estrogen actions of estrogen-dependent human tissues. STS and EST, however, have not been studied in detail in the human vascular system associated with atherosclerotic changes. Therefore, the relative abundance of STS- and EST-immunoreactive protein and mRNA expression in human aorta were evaluated using immunohistochemistry and reverse transcription followed by quantitative polymerase chain reaction in addition to enzyme activity. Furthermore, we evaluated the relative abundance of messenger RNA (mRNA) of both ER subtypes (ERα and ERβ) in the human aorta using reverse transcription followed by quantitative polymerase chain reaction (RT-qPCR), as well as the immunoreactivity of both ERs in VSMCs of human atherosclerotic lesions. STS expression levels were found to be significantly higher in the VSMCs obtained from female aortas with mild atherosclerotic changes than in those with severe atherosclerotic changes and in male aortas regardless of atherosclerotic changes. EST expression levels in the VSMCs of these aortas, however, were significantly higher in female aortas with severe atherosclerotic changes and in male aortas than in female aortas with mild atherosclerotic changes. In addition, the number of ERα and/or ERβ double positive cells in the neointima was higher in female aortas with a mild degree of atherosclerosis than in female aortas with severe atherosclerosis. They indicate that both abundance of these estrogen-metabolizing enzymes in female aorta and relative levels of ER in VSMCs of female neointima may be associated with the status of atherosclerotic changes.

本文言語English
ページ(範囲)263-268
ページ数6
ジャーナルJournal of Steroid Biochemistry and Molecular Biology
93
2-5
DOI
出版ステータスPublished - 2005 2

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 分子医療
  • 分子生物学
  • 内分泌学
  • 臨床生化学
  • 細胞生物学

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