The role of estrogen receptor subtypes for vascular maintenance

Protective role of estrogens (E2) against cardiovascular disease has been appreciated for many years until the equivocal results of cardiovascular outcomes in clinical trials on hormone replacement therapy were reported. Although new ongoing trials aim to resolve these discrepancies, it is obvious that cardiovascular effects of E(2) are complex and diverse. To understand further the cardiovascular effects of E(2), the detailed knowledge on the specific role of both classical estrogen receptor (ER) subtypes and G protein-coupled receptor-30 in the vasculature are of importance. In this article, we review the current knowledge about the pattern of ERalpha and ERbeta expression in human vasculature, the genomic and non-genomic cardiovascular effects of E(2)versus subtype selective ERalpha and ERbeta stimulation on isolated arteries and in different knockout animal models. The results indicate that although ERalpha and ERbeta are expressed in the endothelium and media of human arteries, there is no definite evidence for predominant expression of one over another, the pattern depends on vascular bed, sex and diseased condition. Data from the experiments on isolated arteries and in ER knockout animal models may indicate that activation of specific ER subtypes could provide additional cardiovascular protective effects. However, a clear role for each ERs have to be finalised with focus on mechanisms and by exploring the potential of ERs-selective agonists for clinical utility.