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An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Estrogen improves vascular function via peroxisome-proliferator-activated-receptor-γ
Vedat Tiyerili1, Cornelius F H Müller, Stephen Fung
1Medizinische Klinik und Poliklinik II, Innere Medizin, Universitätsklinikum Bonn, Sigmund Freud Str. 25, 53105 Bonn, Germany.
Journal of Molecular and Cellular Cardiology
|May 29, 2012
Summary
Estrogen
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Molecular Medicine
Background:
- The precise role of estrogen in cardiovascular disease remains unclear.
- Estrogen receptors (ERs) and peroxisome-proliferator-activated-receptor-γ (PPARγ) are nuclear receptors involved in regulating genes that protect against atherosclerosis.
- PPARγ is implicated in the vascular effects of estrogen.
Purpose of the Study:
- To determine if estrogen's vascular effects are mediated by PPARγ regulation within the vasculature.
- To investigate the link between estrogen, PPARγ expression, and cardiovascular health.
Main Methods:
- Studied estrogen-deficient ovariectomized (OVX) wildtype and ApoE(-/-) mice.
- Administered 17ß-estradiol hormone replacement therapy to OVX mice.
- Utilized a PPARγ antagonist (GW9662) and a PPARγ agonist (pioglitazone) to assess PPARγ's role.
- Measured PPARγ expression, reactive oxygen species (ROS) generation, monocyte recruitment, endothelial function, and atherosclerotic lesion formation.
Main Results:
- Estrogen deficiency in OVX mice led to reduced PPARγ expression in aortic tissue.
- 17ß-estradiol replacement therapy increased vascular PPARγ expression and improved endothelial function.
- In estrogen-deficient ApoE(-/-) mice, low PPARγ expression correlated with ROS generation, endothelial dysfunction, and atherogenesis.
- Estrogen replacement in OVX ApoE(-/-) mice restored PPARγ expression, reduced ROS, monocyte recruitment, and atherosclerosis, while improving endothelial function.
- PPARγ antagonism diminished estrogen's beneficial vascular effects.
- PPARγ agonism in estrogen-deficient mice improved vascular morphology and function.
Conclusions:
- 17ß-estradiol actively regulates vascular PPARγ expression in both wildtype and ApoE(-/-) mice.
- PPARγ serves as a crucial downstream target for estrogen's anti-inflammatory and atheroprotective actions in the vascular wall.
- These effects are independent of modifications to traditional cardiovascular risk factors.
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