US EPA

9892220 

Journal Article 

[The nuclear receptor NOR-1 regulates the activation of vascular cells and vascular remodelling in response to hemodynamic stress] 

Rodriguez-Calvo, R; Guadall, A; Calvayrac, O; Alonso, J; Ferran, B; Marti, I; Navarro, MÁ; de Diego, A; Osada, J; Rodríguez, C; Martínez-González, J 

2014 

26 

2 

66-75 

Spanish 

24630523 

10.1016/j.arteri.2013.11.001 

INTRODUCTION: Previous studies have shown that the loss of NOR-1 function modulates the activation of vascular smooth muscle cells (VSMC). In this study we use a mouse that over-expresses human NOR-1 in VSMC to analyze the effect of a gain of NOR-1 function on the activation of VSMC and in the hyperplasia of the intima induced by hemodynamic stress.

METHODS: To generate the transgenic animal the human NOR-1 cDNA was placed under the control of the SM22α promoter. The expression of NOR-1 was analyzed by real time PCR, Western blot, immunohistochemistry and immunocitochemistry, and NOR-1 functionality was evaluated by luciferase activity assays. The incorporation of tritiated thymidine was determined as a cell proliferation index. The left carotid artery was ligated, and cross-sections were subjected to morphometric and immunostaining analysis.

RESULTS: The transgenic mouse exhibited significant levels of human NOR-1 in aorta and carotid arteries. In aortic VSMC from transgenic mice an increase in the transcriptional activity of ciclin D2 was detected, as well as higher proliferative rates and increased levels of the marker Myh10. In these animals, carotid artery ligation induced a greater neointimal formation and a higher stenotic grade than in wild-type animals, in accordance with the labelling detected for Myh10 and phosphorylated Histone H3.

CONCLUSIONS: These results reinforce the role of NOR-1 in VSMC proliferation and in vascular remodelling, and allow us to propose this model as a useful tool to study the involvement of NOR-1 in vascular function and in vascular diseases such as atherosclerosis and restenosis.