J. Lipid Res.
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A more recent version of this article appeared on January 1, 2003

Papers In Press, published online ahead of print October 1, 2002
J. Lipid Res., doi:10.1194/jlr.M100440-JLR200
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Submitted on December 27, 2001
Revised on July 12, 2002
Accepted on September 19, 2002

Cholesteryl ester transfer protein expression attenuates atherosclerosis in ovariectomized mice

Patricia M. Cazita, Jairo A. Berti, Carolina Aoki, Magnus Gidlund, Lila M. Harada, Valeria S. Nunes, Eder C .R. Quintao, and Helena C .F. Oliveira

Fisiologia e Biofisica, Universidade Estadual de Campinas, Campinas, Sao Paulo 13083-970

Corresponding Author: ho98{at}unicamp.br

Reduced estrogen levels result in loss of protection from coronary heart disease among 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 to 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 two-fold larger in OV CETP- than in OV CETP+ mice (147 ± 90 vs 73 ± 42 x 103 µm2, 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 to OV CETP- macrophages. These findings support the proposed anti-atherogenic role of CETP in specific metabolic settings.


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