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Originally published In Press as doi:10.1194/jlr.M100440-JLR200 on October 1, 2002

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Journal of Lipid Research, Vol. 44, 33-40, January 2003
Copyright © 2003 by Lipid Research, Inc.

Cholesteryl ester transfer protein expression attenuates atherosclerosis in ovariectomized mice

Patrícia M. Cazita*, Jairo A. Berti{dagger}, Carolina Aoki{dagger}, Magnus Gidlund§, Lila M. Harada*, Valéria S. Nunes*, Eder C. R. Quintão* and Helena C. F. Oliveira1,{dagger}

* Laboratório de Lípides, Faculdade de Medicina da Universidade de São Paulo, 01246-903, SP, Brazil
{dagger} Departamento Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, 13083-970, SP, Brazil
§ Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, 05508-900, SP, Brazil

1 To whom correspondence should be addressed. e-mail: ho98{at}unicamp.br

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 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 with OV CETP- macrophages.

These findings support the proposed anti-atherogenic role of CETP in specific metabolic settings.

Supplementary key words LDL receptor knockout mice • CETP transgenic mice • lecithin cholesterol acyl transferase • oxidized LDL • phospholipid transfer protein • estrogen


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