Print Email Facebook Twitter Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice Title Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice Author van der Hoorn, J.W.A. de Haan, W. Berbée, J.P.P. Havekes, L.M. Jukema, J.W. Rensen, P.C. Princen, H.M.G. TNO Kwaliteit van Leven Publication year 2008 Abstract Objective - Niacin potently decreases plasma triglycerides and LDL-cholesterol. In addition, niacin is the most potent HDL-cholesterol- increasing drug used in the clinic. In the present study, we aimed at elucidation of the mechanism underlying its HDL-raising effect. Methods and Results - InAPOE*3Leiden transgenic mice expressing the human CETP transgene, niacin dose-dependently decreased plasma triglycerides (up to -77%, P<0.001) and total cholesterol (up to -66%, P<0.001). Concomitantly, niacin dose-dependently increased HDL-cholesterol (up to +87%, P<0.001), plasma apoAI (up to +72%, P<0.001), as well as the HDL particle size. In contrast, in APOE*3Leiden mice, not expressing CETP, niacin also decreased total cholesterol and triglycerides but did not increase HDL-cholesterol. In fact, in APOE*3Leiden.CETP mice, niacin dose-dependently decreased the hepatic expression of CETP (up to -88%; P<0.01) as well as plasma CETP mass (up to -45%, P<0.001) and CETP activity (up to -52%, P<0.001). Additionally, niacin dose-dependently decreased the clearance of apoAI from plasma and reduced the uptake of apoAI by the kidneys (up to -90%, P<0.01). Conclusion - Niacin markedly increases HDL-cholesterol in APOE*3Leiden. CETP mice by reducing CETP activity, as related to lower hepatic CETP expression and a reduced plasma (V)LDL pool, and increases HDL-apoAI by decreasing the clearance of apoAI from plasma. © 2008 American Heart Association, Inc. Subject APOE*3Leiden.CETP transgenic miceCETPHDL-cholesterolHyperlipidemiaNiacincholesterolcholesterol ester transfer proteinhigh density lipoproteinhigh density lipoprotein cholesterollow density lipoprotein cholesterolnicotinic acidtriacylglycerolantilipemic agentCETP protein, humanmessenger RNAanimal experimentanimal modelanimal tissueblood levelcholesterol blood levelcontrolled studydose responsedrug dose comparisondrug mechanismfemalegene activitygene expression regulationhypercholesterolemiahypertriglyceridemiakidneylipid transportlipoprotein blood levellivermousemouse strainnonhumanparticle sizeplasma clearancepriority journalprotein blood levelprotein functionprotein transporttransgenic mousetriacylglycerol blood levelatherosclerosisbilebloodchemistrydisease modeldrug effectfat intakefecesgeneticsmetabolismtimeupregulationAnimalsAntilipemic AgentsApolipoprotein A-IApolipoprotein E3AtherosclerosisBileCholesterol Ester Transfer ProteinsCholesterol, HDLDietary FatsDisease Models, AnimalDose-Response Relationship, DrugFecesFemaleHumansLiverMiceMice, TransgenicNiacinRNA, MessengerTime FactorsTriglyceridesUp-Regulation To reference this document use: http://resolver.tudelft.nl/uuid:b9bd424b-e276-41d9-8784-f05556a93eb6 DOI https://doi.org/10.1161/atvbaha.108.171363 TNO identifier 241104 ISSN 1079-5642 Source Arteriosclerosis, Thrombosis, and Vascular Biology, 28 (11), 2016-2022 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.