| Autor: |
Watanabe, Tokumitsu, Akishita, Masahiro, Nakaoka, Takashi, Kozaki, Koichi, Miyahara, Yukiko, He, Hong, Ohike, Yumiko, Ogita, Teruhiko, Inoue, Satoshi, Muramatsu, Masami, Yamashita, Naohide, Ouchi, Yasuyoshi |
| Předmět: |
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| Zdroj: |
Cardiovascular Research; Sep2003, Vol. 59 Issue 3, p734, 11p |
| Abstrakt: |
Objectives: It has been demonstrated that 17β-estradiol (E2) has an inhibitory effect on the proliferation of vascular smooth muscle cells (VSMCs) through an estrogen receptor (ER)-dependent pathway. Both ER subtypes, classical ER (ERα) and the newly identified ER subtype (ERβ), are expressed in VSMCs. However, it remains unknown which receptor plays the critical role in the inhibitory effect on VSMC proliferation. Methods and results: We constructed replication-deficient adenoviruses bearing the coding region of human ERα, ERβ, and the dominant-negative form of ERβ (designated AxCAERα, AxCAERβ, and AxCADNERβ, respectively). Prior to infection with the adenoviruses, 100 nmol/l E2 attenuated DNA synthesis by up to 14% and transactivated the estrogen-induced expression of the desired mRNA in rat VSMCs. This was accompanied by increased transcriptional activity of estrogen responsive element in response to E2, and the increase was comparable between AxCAERα and AxCAERβ. When VSMCs were infected with AxCAERβ at a multiplicity of infection of 5 or higher, DNA synthesis as well as cell number decreased by 50% in response to E2, and the effect was abolished by co-infection with AxCADNERβ. In contrast, when VSMCs were infected with AxCAERα, the reduction in DNA synthesis was minimal. Conclusions: Our results indicate that ERβ is more potent than ERα in the inhibitory effect on VSMC proliferation. [Copyright &y& Elsevier] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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