Print Email Facebook Twitter Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3-Leiden mice Title Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3-Leiden mice Author Westerterp, M. van der Hoogt, C.C. de Haan, W. Offerman, E.H. Dallinga-Thie, G.M. Jukema, J.W. Havekes, L.M. Rensen, P.C.N. TNO Kwaliteit van Leven Publication year 2006 Abstract OBJECTIVE - The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still undergoing debate. Therefore, we evaluated the effect of human CETP expression on atherosclerosis in APOE*3-Leiden (E3L) mice with a humanized lipoprotein profile. METHODS AND RESULTS - E3L mice were crossbred with human CETP transgenic mice. On a chow diet, CETP expression increased plasma total cholesterol (TC) (+43%; P<0.05). To evaluate the effects of CETP on the development of atherosclerosis, mice were fed a Western-type diet containing 0.25% cholesterol, leading to 4.3-fold elevated TC levels in both E3L and CETP.E3L mice (P<0.01). On both diets, CETP expression shifted the distribution of cholesterol from high-density lipoprotein (HDL) toward very-low-density lipoprotein (VLDL)/low-density lipoprotein (LDL). Moreover, plasma of CETP.E3L mice had reduced capacity (-39%; P<0.05) to induce SR-BI-mediated cholesterol efflux from Fu5AH cells than plasma of E3L mice. After 19 weeks on the Western-type diet, CETP.E3L mice showed a 7.0-fold increased atherosclerotic lesion area in the aortic root compared with E3L mice (P<0.0001). CONCLUSIONS - CETP expression in E3L mice shifts the distribution of cholesterol from HDL to VLDL/LDL, reduces plasma-mediated SR-BI-dependent cholesterol efflux, and represents a clear pro-atherogenic factor in E3L mice. We anticipate that the CETP.E3L mouse will be a valuable model for the preclinical evaluation of HDL-raising interventions on atherosclerosis development. © 2006 American Heart Association, Inc. Chemicals / CAS: cholesterol, 57-88-5; Antigens, CD36; apolipoprotein E3 (Leidein); Apolipoprotein E3; Apolipoproteins E; Carrier Proteins; CETP protein, human; Cholesterol Ester Transfer Proteins; Cholesterol, 57-88-5; Glycoproteins; Lipids; Lipoproteins; Lipoproteins, HDL Subject HealthBiomedical ResearchCETPCholesterol effluxHyperlipidemiaReverse cholesterol transportTransgenic mice cholesterolHigh density lipoproteinLow density lipoproteinVery low density lipoproteinAnimal cellAnimal experimentAnimal modelAnimal tissueAorta rootAtherosclerosisCholesterol blood levelControlled studyDietMouseNonhumanPlasmaProtein expressionTransgenic mouseAnimalsAntigens, CD36Apolipoprotein E3Apolipoproteins EAtherosclerosisCarrier ProteinsCell Line, TumorCholesterolCholesterol Ester Transfer ProteinsDietFemaleGlycoproteinsHumansLipidsLipoproteinsLipoproteins, HDLMacrophagesMiceMice, TransgenicRats To reference this document use: http://resolver.tudelft.nl/uuid:d08a0940-e4b4-40fa-814f-7107891d1ed3 DOI https://doi.org/10.1161/01.atv.0000243925.65265.3c TNO identifier 239562 ISSN 1079-5642 Source Arteriosclerosis, Thrombosis, and Vascular Biology, 26 (11), 2552-2559 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.