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Cholesteryl ester transfer protein expression attenuates atherosclerosis in ovariectomized mice
Patrícia M Cazita1, Jairo A Berti, Carolina Aoki
1Laboratório de Lípides, Faculdade de Medicina da Universidade de São Paulo, 01246-903, SP, Brazil.
Journal of Lipid Research
|January 9, 2003
Summary
Cholesteryl ester transfer protein (CETP) plays an anti-atherogenic role in postmenopausal mice, reducing coronary heart disease risk. Estrogen therapy further enhances CETP
Area of Science:
- Cardiovascular Science
- Endocrinology
- Lipid Metabolism
Background:
- Postmenopausal women lose estrogen's cardioprotective effects, increasing coronary heart disease risk.
- Cholesteryl ester transfer protein (CETP) levels correlate with atherosclerosis, but its interaction with ovarian hormones is unclear.
- Understanding CETP's role in atherogenesis alongside hormonal changes is crucial for cardiovascular health.
Purpose of the Study:
- To investigate the interplay between cholesteryl ester transfer protein (CETP) and ovarian hormones in diet-induced atherosclerosis.
- To assess the impact of CETP expression and estrogen therapy on lipid profiles and lesion development in mice.
- To elucidate the mechanisms by which CETP and estrogen influence macrophage lipid uptake and cholesterol efflux.
Main Methods:
- Utilized ovariectomized (OV) CETP transgenic mice crossbred with LDL receptor knockout mice to model postmenopausal atherosclerosis.
- Administered estrogen therapy to OV mice to evaluate its effects on plasma lipoproteins, oxidized LDL antibodies, and aortic lesion size.
- Assessed macrophage cholesteryl ether uptake and HDL-mediated cholesterol efflux in relation to CETP expression and estrogen treatment.
Main Results:
- OV CETP non-expressing mice exhibited significantly larger aortic lesion areas compared to OV CETP-expressing mice.
- CETP non-expression was associated with higher plasma total, VLDL-, LDL-, and HDL-cholesterol, and increased antibodies against oxidized LDL.
- Estrogen therapy reduced atherosclerosis severity and normalized lipid profiles, blunting CETP-dependent differences; it also decreased macrophage cholesteryl ether uptake and enhanced cholesterol efflux in CETP-expressing mice.
Conclusions:
- Cholesteryl ester transfer protein (CETP) demonstrates an anti-atherogenic effect in the context of reduced estrogen levels.
- Estrogen therapy complements CETP's protective role by modulating lipid metabolism and macrophage function.
- These findings highlight CETP's potential as a therapeutic target for cardiovascular disease in postmenopausal women.