Identification and Characterization of New Mechanisms in Vascular Estrogen Signalling.

Estrogen 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 estrogen-evoked beneficial effects have been attributed to estrogen receptor α (ERα), also ERβ and the novel ER GPR30/GPER1 probably play significant roles in vascular estrogen signalling. Estrogen-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 estrogen treatment and the clinical findings on hormone replacement therapy obtained in big epidemiology surveys, where no protective effect from supplementation with estrogen 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 estrogen-evoked beneficial effects in vascular health and disease. Importantly, some vascular effects of pharmacological concentrations of estrogen are ER-independent, suggesting that estrogen besides its specific effects through ERα, ERβ and GPR30 also affects vascular function via ER-independent mechanisms probably reflecting interaction of the hydrophobic estrogen molecule with cell membrane properties. In this MiniReview, we focus on the importance of these different vascular ER subtypes in health and disease. This article is protected by copyright. All rights reserved