Print Email Facebook Twitter Atorvastatin increases HDL cholesterol by reducing CETP expression in cholesterol-fed APOE*3-Leiden.CETP mice Title Atorvastatin increases HDL cholesterol by reducing CETP expression in cholesterol-fed APOE*3-Leiden.CETP mice Author de Haan, W. van der Hoogt, C.C. Westerterp, M. Hoekstra, M. Dallinga-Thie, G.M. Princen, H.M.G. Romijn, J.A. Jukema, J.W. Havekes, L.M. Rensen, P.C.N. TNO Kwaliteit van Leven Publication year 2008 Abstract Objective: In addition to lowering low-density lipoprotein (LDL)-cholesterol, statins modestly increase high-density lipoprotein (HDL)-cholesterol in humans and decrease cholesteryl ester transfer protein (CETP) mass and activity. Our aim was to determine whether the increase in HDL depends on CETP expression. Methods and results: APOE*3-Leiden (E3L) mice, with a human-like lipoprotein profile and a human-like responsiveness to statin treatment, were crossbred with mice expressing human CETP under control of its natural flanking regions resulting in E3L.CETP mice. E3L and E3L.CETP mice were fed a Western-type diet with or without atorvastatin. Atorvastatin (0.01% in the diet) reduced plasma cholesterol in both E3L and E3L.CETP mice (-26 and -33%, P < 0.05), mainly in VLDL, but increased HDL-cholesterol only in E3L.CETP mice (+52%). Hepatic mRNA expression levels of genes involved in HDL metabolism, such as phospholipid transfer protein (Pltp), ATP-binding cassette transporter A1 (Abca1), scavenger receptor class B type I (Sr-b1), and apolipoprotein AI (Apoa1), were not differently affected by atorvastatin in E3L.CETP mice as compared to E3L mice. However, in E3L.CETP mice, atorvastatin down-regulated the hepatic CETP mRNA expression (-57%; P < 0.01) as well as the total CETP level (-29%) and cholesteryl esters (CE) transfer activity (-36%; P < 0.05) in plasma. Conclusions: Atorvastatin increases HDL-cholesterol in E3L.CETP mice by reducing the CETP-dependent transfer of cholesterol from HDL to (V)LDL, as related to lower hepatic CETP expression and a reduced plasma (V)LDL pool. © 2007 Elsevier Ireland Ltd. All rights reserved. Subject HealthCETPHigh-density lipoproteinHMGCoA reductaseStatinTransgenic miceABC transporter A1apolipoprotein A1apolipoprotein E3atorvastatincholesterol ester transfer proteinhigh density lipoproteinhigh density lipoprotein cholesterolmessenger RNAphospholipid transfer proteinscavenger receptor BIvery low density lipoproteinvery low density lipoprotein cholesterolanimal experimentanimal modelarticlecholesterol blood levelcholesterol dietcontrolled studydrug effectgene expressionhypercholesterolemialipoprotein blood levellipoprotein metabolismmalemousenonhumanpriority journalprotein expressiontransgenic mouseAnimalsApolipoprotein E3Cholesterol Ester Transfer ProteinsCholesterol, DietaryCholesterol, HDLCholesterol, VLDLDose-Response Relationship, DrugFemaleGene ExpressionHeptanoic AcidsHumansHydroxymethylglutaryl-CoA Reductase InhibitorsHypercholesterolemiaLiverMaleMiceMice, Inbred C57BLMice, TransgenicPyrrolesRNA, Messenger To reference this document use: http://resolver.tudelft.nl/uuid:b1f12e01-d3a5-45f5-9333-01c50d94ab73 DOI https://doi.org/10.1016/j.atherosclerosis.2007.08.001 TNO identifier 240676 ISSN 0021-9150 Source Atherosclerosis, 197 (1), 57-63 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.