title: Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice.
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.
  
  
  RESULTS
  In APOE*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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Netherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands. jose.vanderhoorn@tno.nl
authors.forename: José W A
authors.initials: JW
authors.lastname: van der Hoorn
authors.forename: Willeke
authors.initials: W
authors.lastname: de Haan
authors.forename: Jimmy F P
authors.initials: JF
authors.lastname: Berbée
authors.forename: Louis M
authors.initials: LM
authors.lastname: Havekes
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
authors.forename: Hans M G
authors.initials: HM
authors.lastname: Princen
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D053318:Apolipoprotein E3 / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009525:Niacin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation
chemical_list: D016632:Apolipoprotein A-I; D053318:Apolipoprotein E3; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D004041:Dietary Fats; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D014280:Triglycerides; D009525:Niacin