Identification and characterization of new mechanisms in vascular oestrogen signalling

Oestrogen exerts vasculoprotective effects in different experimental settings through inhibition of vascular smooth muscle cell proliferation, stimulation of nitric oxide production and attenuation of inflammation. Although these oestrogen-evoked beneficial effects have been attributed to oestrogen receptor alpha (ERα), also ER beta (ERβ) and the novel ER G protein-coupled receptor 30 (GPR30)/G protein-coupled ER1 probably play significant roles in vascular oestrogen signalling. Oestrogen-evoked vasculoprotective effects are well documented in various experimental models, but the underlying mechanisms are still incompletely understood. The age hypothesis represents an interesting and promising model to explain the discrepancy between experimental data showing beneficial vascular effects of oestrogen treatment and the clinical findings on hormone replacement therapy obtained in big epidemiology surveys, where no protective effect from supplementation with oestrogen is observed. Identification of novel ERs expressed also in the vascular system offers exciting opportunities for the future to find and characterize the mechanisms behind oestrogen-evoked beneficial effects in vascular health and disease. Importantly, some vascular effects of pharmacological concentrations of oestrogen are ER-independent, suggesting that oestrogen besides its specific effects through ERα, ERβ and GPR30 also affects vascular function via ER-independent mechanisms probably reflecting interaction of the hydrophobic oestrogen molecule with cell membrane properties. In this MiniReview, we focus on the importance of these different vascular ER subtypes in health and disease.