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Publication : Cholesteryl ester transfer protein expression attenuates atherosclerosis in ovariectomized mice.

First Author  Cazita PM Year  2003
Journal  J Lipid Res Volume  44
Issue  1 Pages  33-40
PubMed ID  12518020 Mgi Jnum  J:120685
Mgi Id  MGI:3707650 Doi  10.1194/jlr.m100440-jlr200
Citation  Cazita PM, et al. (2003) Cholesteryl ester transfer protein expression attenuates atherosclerosis in ovariectomized mice. J Lipid Res 44(1):33-40
abstractText  Reduced estrogen levels result in loss of protection from coronary heart disease in postmenopausal women. Enhanced and diminished atherosclerosis have been associated with plasma levels of cholesteryl ester transfer protein (CETP); however, little is known about the role of CETP-ovarian hormone interactions in atherogenesis. We assessed the severity of diet-induced atherosclerosis in ovariectomized (OV) CETP transgenic mice crossbred with LDL receptor knockout mice. Compared with OV CETP expressing ((+)), OV CETP non-expressing ((-)) mice had higher plasma levels of total, VLDL-, LDL-, and HDL-cholesterol, as well as higher antibodies titers against oxidized LDL. The mean aortic lesion area was 2-fold larger in OV CETP(-) than in OV CETP(+) mice (147 +/- 90 vs. 73 +/- 42 x 10(3) micro m(2), respectively). Estrogen therapy in OV mice blunted the CETP dependent differences in plasma lipoproteins, oxLDL antibodies, and atherosclerosis severity. Macrophages from OV CETP(+) mice took up less labeled cholesteryl ether (CEt) from acetyl-LDL than macrophages from OV CETP(-) mice. Estrogen replacement induced a further reduction in CEt uptake and an elevation in HDL mediated cholesterol efflux from pre-loaded OV CETP(+) as compared with OV CETP(-) macrophages. These findings support the proposed anti-atherogenic role of CETP in specific metabolic settings.
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