Fiche publication
Date publication
mars 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
Tous les auteurs :
Hogg ME, Vavra AK, Banerjee MN, Martinez J, Jiang Q, Keefer LK, Chambon P, Kibbe MR
Lien Pubmed
Résumé
BACKGROUND: We previously demonstrated that vascular smooth muscle cells (VSMC) proliferation and development of neointimal hyperplasia as well as the ability of nitric oxide (NO) to inhibit these processes is dependent on sex and hormone status. The aim of this study was to evaluate the role of estrogen receptor (ER) in mediating proliferation in male and female VSMC. MATERIALS AND METHODS: Proliferation was assessed in primary rat aortic male and female VSMC using (3)H-thymidine incorporation in the presence or absence of ER alpha (alpha) inhibitor methyl-piperidino-pyrazole, the ER beta (beta) inhibitor (R,R)-5,11-Diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol, the combined ERalphabeta inhibitor ICI 182,780, and/or the NO donor DETA/NO. Proliferation was also assessed in primary aortic mouse VSMC harvested from wildtype (WT), ERalpha knockout (ERalpha KO), and ERbeta knockout (ERbeta KO) mice in the presence or absence of DETA/NO and the ERalpha, ERbeta, and ERalphabeta inhibitors. Protein levels were assessed using Western blot analysis. RESULTS: Protein expression of ERalpha and ERbeta was present and equal in male and female VSMC, and did not change after exposure to NO. Inhibition of either ERalpha or ERbeta had no effect on VSMC proliferation in the presence or absence of NO in either sex. However, inhibition of ERalphabeta in rat VSMC mitigated NO-mediated inhibition in female but not male VSMC (P < 0.05). Evaluation of proliferation in the knockout mice revealed distinct patterns. Male ERalphaKO and ERbetaKO VSMC proliferated faster than male WT VSMC (P < 0.05). Female ERbetaKO proliferated faster than female WT VSMC (P < 0.05), but female ERalphaKO VSMC proliferated slower than female WT VSMC (P < 0.05). Last, we evaluated the effect of combined inhibition of ERalpha and ERbeta in these knockout strains. Combined ERalphabeta inhibition abrogated NO-mediated inhibition of VSMC proliferation in female WT and knockout VSMC (P < 0.05), but not in male VSMC. CONCLUSIONS: These data clearly demonstrate a role for the ER in mediating VSMC proliferation in both sexes. However, these data suggest that the antiproliferative effects of NO may be regulated by the ER in females but not males.
Référence
J Surg Res. 2012 Mar;173(1):e1-10
