Cholesteryl ester transfer protein expression attenuates atherosclerosis in ovariectomized mice.

Abstract:

: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.

journal_name

J Lipid Res

authors

Cazita PM,Berti JA,Aoki C,Gidlund M,Harada LM,Nunes VS,Quintão EC,Oliveira HC

doi

10.1194/jlr.m100440-jlr200

keywords:

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

33-40

issue

1

eissn

0022-2275

issn

1539-7262

journal_volume

44

pub_type

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