Loss-of-function deletion of the steroid receptor coactivator-1 gene in mice reduces estrogen effect on the vascular injury response.
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.


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.
Yuan
Yuhui
Y
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Xu
Jianming
J
D000818:Animals; D015153:Blotting, Western; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D056920:Nuclear Receptor Coactivator 1; D010052:Ovariectomy; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D014157:Transcription Factors; D004958:Estradiol; D051548:Histone Acetyltransferases; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1