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Updated: Jun 22, 2026
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Inhibitory effect of estrogen on Rac1-expression in monocytes
Oliver Adam1, Marion Hagel, Katharina Theobald
1Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, D-66421 Homburg/Saar, Germany. oliver.adam@uks.eu
Abstract:
Recruitment of circulating monocytes into the vasculature and release of reactive oxygen species (ROS) promote atherogenesis. Rac1-GTPase is an essential component of the superoxide-producing NADPH-oxidase complex. Estrogens inhibit production of vascular reactive oxygen species. Angiotensin II as well as overexpression of the constitutively active mutant RacL61 increased ROS production in monocytes. AngII-mediated ROS release was completely inhibited by overexpression of the dominant negative mutant RacN17 or treatment with 17beta-estradiol. 17beta-Estradiol reduced Rac1-expression concentration- and time-dependently and decreased basal, as well as AngII-induced Rac1 activity. The effects of 17beta-estradiol were receptor-mediated. In vivo, down-regulation of Rac1 by 17beta-estradiol was observed in human mononuclear cells of women with elevated 17beta-estradiol levels after controlled ovarian hyperstimulation. In summary, the data show that down-regulation of Rac1-GTPase contributes to the inhibition of angiotensin II-mediated superoxide release by 17beta-estradiol in monocytes.
Insights
Estrogen (17beta-estradiol) inhibits reactive oxygen species (ROS) production in monocytes by reducing Rac1-GTPase activity. This finding suggests a mechanism by which estrogen protects against atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Endocrinology
Background:
- Monocyte recruitment and reactive oxygen species (ROS) production are key drivers of atherogenesis.
- Rac1-GTPase is crucial for the NADPH-oxidase complex, which generates ROS.
- Estrogens are known to inhibit vascular ROS production.
Purpose of the Study:
- To investigate the role of Rac1-GTPase in angiotensin II-induced ROS production in monocytes.
- To determine the effect of 17beta-estradiol on Rac1 activity and expression.
- To elucidate the mechanism by which estrogen inhibits ROS production in monocytes.
Main Methods:
- Monocytes were treated with Angiotensin II (AngII) and/or 17beta-estradiol.
- Rac1 activity and expression were assessed using dominant-negative RacN17 and constitutively active RacL61 mutants.
- In vivo studies involved human mononuclear cells from women undergoing controlled ovarian hyperstimulation.
Main Results:
- AngII and RacL61 overexpression increased ROS production in monocytes.
- 17beta-estradiol completely inhibited AngII-mediated ROS release.
- 17beta-estradiol reduced Rac1 expression and activity in a concentration- and time-dependent manner.
- Estrogen's effects were receptor-mediated and observed in vivo.
Conclusions:
- Down-regulation of Rac1-GTPase by 17beta-estradiol contributes to the inhibition of AngII-induced superoxide release in monocytes.
- Estrogen signaling pathways may offer therapeutic targets for preventing or treating atherosclerosis.
