Role of Estrogen Receptor GPER for Toll-Like Receptor 4-Dependent Inflammatory Activation in Atherosclerosis
Description: Lead<BR>Estrogens protect from vascular diseases in part by improving the function of endothelial cells, the innermost cell layer of the vascular wall. This study investigates whether the G protein-coupled estrogen receptor GPER mediates protective effects on endothelial cell function.<BR><BR>Background<BR>In healthy blood vessels, normal endothelial cell function is maintained by a balanced release of vasodilator factors such as nitric oxide (NO), and vasoconstrictor factors such as endothelin-1 (ET-1) and other endothelium-derived contracting factors (EDCF). In diseased arteries, endothelial NO bioactivity is impaired, which favors vasoconstrictor effects and disease progression. Estrogens are sex hormones that protect premenopausal women from vascular disease, in part by improving endothelial cell function. Biologic effects of estrogens are mediated via activation of multiple estrogen receptors. It is unclear, however, whether endogenous GPER regulates endothelium-dependent vascular reactivity.<BR><BR>Key Results<BR>This study shows that GPER regulates endothelial cell bioactivity of NO, ET-1, and EDCF. Using GPER-deficient mice and a GPER-selective agonist and antagonist, it identifies GPER as an estrogen receptor with inhibitory activity on ET-1- and EDCF-dependent contractility, while improving NO bioactivity under certain conditions.<BR><BR>Significance<BR>Conditions such as aging, high blood pressure, and obesity accelerate vascular disease development and are associated with increased endothelium-dependent vasoconstriction and reduced NO bioactivity. The ability of GPER to mitigate the vasoconstrictor effects of ET-1 and EDCF and to enhance NO bioactivity suggests a therapeutic potential of selective GPER activation in the presence of vascular diseases. Using an atherosclerosis model, this will be investigated during the continuation of this fellowship (PBZHP3-141501).<BR>
Amount: CHF 59,800
Funding type: fellowship
Funder scheme: Fellowships for prospective researchers
Start date: 2011-02-01
End date: 2012-01-31
Investigator: Meyer, Matthias
Institution: Institution abroad - United States of America
Funded outputs count: 19
Funder award ID: 135874
OpenAlex ID: G3201580287