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.
Highlights
Reduced estrogen levels result in loss of protection from coronary heart disease in postmenopausal women
Studies in cholesteryl ester transfer protein (CETP) transgenic mice have shown that CETP expression in the wild-type background is atherogenic in males [5] but not in females [8] or in animal heterozygotes for LDL receptor (LDLR) deficiency
CETP expression is atheroprotective in hypertriglyceridemia [7] and when there is overexpression of Lecithin cholesterol acyl transferase (LCAT) [8]; when cholesterol fed rabbits are used as the experimental model, the inhibition of CETP activity by antisense oligonucleotides [9], chemical inhibitors [10], or vaccination against CETP [11] decreases the atherosclerotic areas by 25%, 67%, and 40%, respectively, compared with control animals
Summary
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); little is known about the role of CETPovarian hormone interactions in atherogenesis. 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. Estrogen therapy in OV mice blunted the CETP dependent differences in plasma lipoproteins, oxLDL antibodies, and atherosclerosis severity. 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 antiatherogenic role of CETP in specific metabolic settings.— Cazita, P.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
