Role of G Protein-Coupled Estrogen Receptor for Endothelial Function and Vascular Inflammation in Early Atherosclerosis
Description: <p><strong>Key results</strong><br />Atherosclerosis is a chronic disease of arterial blood vessels and associated with vascular inflammation and reduced bioactivity of nitric oxide (NO), a gas centrally implicated in protection from atherosclerosis and inflammation. To investigate the role of GPER in atherosclerosis, we fed an atherogenic diet to genetically modified female mice that express or lack the GPER gene. Compared to mice with the GPER gene, atherosclerosis progression and vascular inflammation were increased while NO bioactivity was reduced in mice lacking GPER, revealing an atheroprotective function of GPER. Surgical removal of the ovaries to induce an estrogen-deficient state (a model of menopause) in some cases aggravated these effects. Treatment of estrogen-deficient mice with G-1, a highly selective synthetic drug that activates GPER, reduced atherosclerosis and inflammation. Importantly, G-1 had no stimulating effect on the uterus, a common complication that increases the risk of uterine cancer when natural estrogens are used as hormone therapy in women after menopause.</p><p><strong>Significance</strong><br />Atherosclerotic vascular disease is the leading cause of death in women after menopause. Attempts to reduce the increased risk of postmenopausal atherosclerosis with the use of estrogens as hormone therapy have been disappointing and even associated with adverse effects such as an increased risk of uterine cancer. The concept of selective GPER activation introduced in the present project could be considered as a novel therapeutic strategy for the treatment of atherosclerotic vascular disease in postmenopausal women without stimulating effects on the uterus.</p>
Amount: CHF 58,850
Funding type: fellowship
Funder scheme: Fellowships for prospective researchers
Start date: 2012-02-01
End date: 2013-01-31
Investigator: Meyer, Matthias
Institution: Institution abroad - United States of America
Funded outputs count: 14
Funder award ID: 141501
OpenAlex ID: G8440112380