This Article Full Text Full Text (PDF) All Versions of this Article: 27/7/1521    most recent ATVBAHA.107.144477v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yuan, Y. Articles by Xu, J. Search for Related Content PubMed PubMed Citation Articles by Yuan, Y. Articles by Xu, J.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1521.)
© 2007 American Heart Association, Inc.

Vascular Biology

Loss-of-Function Deletion of the Steroid Receptor Coactivator-1 Gene in Mice Reduces Estrogen Effect on the Vascular Injury Response

Yuhui Yuan; Jianming Xu

From the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Tex.

Correspondence to Jianming Xu, PhD, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail jxu{at}bcm.tmc.edu

Objective— The steroid receptor coactivator-1 (SRC-1) is a transcriptional coactivator for nuclear receptors including estrogen receptor (ER). SRC-1 can interact with ER in an estrogen binding-dependent manner to potentiate the transcriptional activity of ER. Previous studies showed that SRC-1 was required for the full function of ER in cultured cells and in the reproductive system. In this study, we have tested the hypothesis that SRC-1 is required for the inhibition of neointima formation by estrogen in a vascular wall.

Methods and Results— The expression of SRC-1 protein in the vascular wall was examined by immunoblotting and immunohistochemistry. Wild-type and SRC-1 null mice were ovariectomized, and then unilateral ligation of the carotid artery was performed to induce neointima growth in these mice. Mice were treated with placebo or estrogen. Neointima growth near the ligation site was examined and quantitatively analyzed. These experiments demonstrated that SRC-1 was expressed in the endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and neointima cells. The neointima growth induced by the ligation of common carotid artery was almost completely inhibited by estrogen in wild-type mice, but was only partially inhibited in SRC-1–null mice. Further analysis revealed that the blunted inhibition of neointima formation by estrogen was attributed to a less inhibition of neointimal cell proliferation.

Conclusions— SRC-1 is expressed in ECs, VSMCs, and neointima cells. SRC-1 expression in these cells facilitates estrogen/ER-mediated vasoprotection through the inhibition of neointima formation after a vascular injury.

Using SRC-1 knockout mice and a common carotid ligation model, we demonstrated that SRC-1 deficiency reduced the inhibitory effect of estrogen on the neointima formation and on the neointimal cell proliferation after a vascular injury. Our results indicate that SRC-1 dysfunction may result in partial impairment of the vasoprotective effect of estrogen.

Key Words: SRC-1 • estrogen • estrogen receptor • carotid artery • neointima

This article has been cited by other articles:

				L. Qin, Z. Liu, H. Chen, and J. Xu The Steroid Receptor Coactivator-1 Regulates Twist Expression and Promotes Breast Cancer Metastasis Cancer Res., May 1, 2009; 69(9): 3819 - 3827. [Abstract] [Full Text] [PDF]

				S. Wang, Y. Yuan, L. Liao, S.-Q. Kuang, J. C.-Y. Tien, B. W. O'Malley, and J. Xu Disruption of the SRC-1 gene in mice suppresses breast cancer metastasis without affecting primary tumor formation PNAS, January 6, 2009; 106(1): 151 - 156. [Abstract] [Full Text] [PDF]