© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Estrogen receptor β mediates the inhibitory effect of estradiol on vascular smooth muscle cell proliferation
aDepartment of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
bDepartment of Geriatric Medicine, Kyorin University School of Medicine, Tokyo 181-8611, Japan
cDepartment of Advanced Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
dDepartment of Cardiovascular Medicine, University of Tokyo, Tokyo 113-8655, Japan
eResearch Center for Genomic Medicine, Saitama Medical School, Saitama 350-1241, Japan
youchi-tky{at}umin.ac.jp
* Corresponding author. Tel.: +81-3-5800-8830; fax: +81-3-5800-6530.
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 (ER
) 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 ER, ERβ, and the dominant-negative form of ERβ (designated AxCAER, 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 AxCAER 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 AxCAER, the reduction in DNA synthesis was minimal. Conclusions: Our results indicate that ERβ is more potent than ER in the inhibitory effect on VSMC proliferation.
KEYWORDS Atherosclerosis; Gene expression; Hormones; Receptors; Smooth muscle
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L.-Y. C. Wing, Y.-C. Chen, Y.-Y. Shih, J.-C. Cheng, Y.-J. Lin, and M. J. Jiang Effects of Oral Estrogen on Aortic ROS-Generating and -Scavenging Enzymes and Atherosclerosis in apoE-Deficient Mice Experimental Biology and Medicine, September 1, 2009; 234(9): 1037 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yuan and J. Xu Loss-of-Function Deletion of the Steroid Receptor Coactivator-1 Gene in Mice Reduces Estrogen Effect on the Vascular Injury Response Arterioscler Thromb Vasc Biol, July 1, 2007; 27(7): 1521 - 1527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Y. Liu, R. C. Christian, M. Ruan, V. M. Miller, and L. A. Fitzpatrick Correlating Androgen and Estrogen Steroid Receptor Expression with Coronary Calcification and Atherosclerosis in Men without Known Coronary Artery Disease J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1041 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Nakamura, K. Igarashi, T. Suzuki, J. Kanno, T. Inoue, C. Tazawa, M. Saruta, T. Ando, N. Moriyama, T. Furukawa, et al. E4F1, a Novel Estrogen-Responsive Gene in Possible Atheroprotection, Revealed by Microarray Analysis Am. J. Pathol., December 1, 2004; 165(6): 2019 - 2031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. M. Miller, D. J. Tindall, and P. Y. Liu Of Mice, Men, and Hormones Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 995 - 997. [Full Text] [PDF]
|
|