Cholesteryl ester transfer protein (CETP) expression protects against diet induced atherosclerosis in SR-BI deficient mice.
OBJECTIVE
To determine whether expression of the human CETP transgene protects against diet-induced atherosclerosis in SR-BI deficient mice.


RESULTS
SR-BI deficient (-/-) mice were crossed with CETP transgenic (CETPtg) mice to produce a colony of SR-BI(-/-) x CETPtg mice in a C57Bl/6 background. Age and sex matched groups of genetically modified and wild-type C57Bl/6 mice were fed a high fat, high cholesterol diet for 22 weeks. In both wild-type and SR-BI(-/-) mice, expression of the CETP transgene reduced the cholesterol content and increased the density of lipoprotein particles in the HDL density range. In SR-BI(-/-) x CETPtg mice, CETP activity inversely correlated with total plasma cholesterol levels and shifted the buoyant HDL typical of SR-BI deficiency toward a more normal density HDL particle. Atherosclerosis at the level of the aortic arch was evident in both male and female SR-BI deficient mice but occurred to a greater extent in the females. Expression of CETP markedly attenuated the development of atherosclerosis in SR-BI deficient mice fed an atherogenic diet (P<0.003).


CONCLUSIONS
Expression of the human CETP transgene protects SR-BI deficient mice from atherosclerosis, consistent with a role for CETP in remodeling HDL and providing an alternative pathway for the selective uptake of HDL-CE by the liver.
Harder
Christopher
C
Lipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, Ottawa, Canada.
Lau
Paulina
P
Meng
Andrew
A
Whitman
Stewart C
SC
McPherson
Ruth
R
D000818:Animals; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D004036:Diet, Atherogenic; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009994:Osmolar Concentration; D051122:Scavenger Receptors, Class B / Q000172:deficiency*; D012737:Sex Factors
C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol