Background The proliferation of vascular smooth muscle cells (VSMCs) is a key event in the development of atherosclerosis. Oestrogen receptor is expressed in VSMCs. In vivo studies have shown that reduced levels of oestrogen receptor associate with atherosclerosis in females. Accordingly, we performed a series of experiments to test the hypothesis that blocking oestrogen receptor could enhance the proliferation of VSMCs in vitro.
Methods and results ICI182, 780, a pure oestrogen receptor antagonist, has been shown to block oestrogen receptor completely. When VSMCs isolated from rat aorta were cultured in the presence of ICI182, 780, the cellular growth augmented significantly in a dose-dependent manner. An increase in proliferating cell nuclear antigen (PCNA)-positive cells was also observed in VSMCs treated with ICI182, 780. Flow cytometry demonstrated that the S-phase progression of cell cycle in the VSMCs was promoted significantly by ICI182, 780, this effect was associated with an increase in cyclin D1 expression.
Conclusions These findings demonstrate that in vitro blockade of oestrogen receptor promotes the growth of VSMCs, suggesting that oestrogen receptor expressed in arteries acts to inhibit the proliferation of VSMCs and play a functional role in atheroprotection. Efforts aiming at enhancing oestrogen receptor expression and/or activity may prove to be an attractive alternative therapy against atherosclerosis.
- Oestrogen receptor