G protein-coupled estrogen receptor protects from atherosclerosis.
- Meyer MR Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
- Fredette NC Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
- Howard TA Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
- Hu C Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
- Ramesh C Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM, USA.
- Daniel C Pathologisches Institut, Universität Erlangen-Nürnberg, Erlangen, Germany.
- Amann K Pathologisches Institut, Universität Erlangen-Nürnberg, Erlangen, Germany.
- Arterburn JB Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM, USA.
- Barton M Molecular Internal Medicine, University of Zürich, Zürich, Switzerland.
- Prossnitz ER Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
- 2014-12-24
Published in:
- Scientific reports. - 2014
Animals
Atherosclerosis
Cholesterol, LDL
Cyclopentanes
Endothelial Cells
Female
Humans
Intracellular Membranes
Mice
Mice, Knockout
Nitric Oxide
Postmenopause
Quinolines
Receptors, Estrogen
Receptors, G-Protein-Coupled
English
Coronary atherosclerosis and myocardial infarction in postmenopausal women have been linked to inflammation and reduced nitric oxide (NO) formation. Natural estrogen exerts protective effects on both processes, yet also displays uterotrophic activity. Here, we used genetic and pharmacologic approaches to investigate the role of the G protein-coupled estrogen receptor (GPER) in atherosclerosis. In ovary-intact mice, deletion of gper increased atherosclerosis progression, total and LDL cholesterol levels and inflammation while reducing vascular NO bioactivity, effects that were in some cases aggravated by surgical menopause. In human endothelial cells, GPER was expressed on intracellular membranes and mediated eNOS activation and NO formation, partially accounting for estrogen-mediated effects. Chronic treatment with G-1, a synthetic, highly selective small molecule agonist of GPER, reduced postmenopausal atherosclerosis and inflammation without uterotrophic effects. In summary, this study reveals an atheroprotective function of GPER and introduces selective GPER activation as a novel therapeutic approach to inhibit postmenopausal atherosclerosis and inflammation in the absence of uterotrophic activity.
- Language
-
- English
- Open access status
- gold
- Identifiers
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- DOI 10.1038/srep07564
- PMID 25532911
- Persistent URL
- https://sonar.ch/global/documents/236266
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