title: Apolipoprotein B-100 and apoA-II kinetics as determinants of cellular cholesterol efflux.
abstract: BACKGROUND
  Cellular cholesterol efflux is a key step in reverse cholesterol transport and may depend on the metabolism of apolipoprotein (apo) B-100, apoA-I, and apoA-II.
  
  
  OBJECTIVE
  We examined the associations between cholesterol efflux and plasma concentrations and kinetics of very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL)-apoB-100, high-density lipoprotein (HDL)-apoA-I, and HDL-apoA-II in men. DESIGN, SUBJECTS, AND METHODS: Thirty men were recruited from the community with a wide range of body mass index. The capacity of plasma and HDL to efflux cholesterol was measured ex vivo. Apolipoprotein kinetics were measured using stable isotope techniques and multicompartmental modeling.
  
  
  RESULTS
  Cholesterol efflux to whole plasma was correlated with plasma levels of cholesterol, triglyceride, apoB-100, insulin, cholesteryl ester transfer protein, and lecithin-cholesterol acyltransferase, body mass index and waist circumference (P < 0.05 in all). Cholesterol efflux was inversely correlated with the fractional catabolic rate (FCR) of VLDL (r = -0.728), IDL (r = -0.662), and LDL-apoB-100 (r = -0.479) but positively correlated with the FCR (r = 0.438) and production rate (r = 0.468) of HDL-apoA-II. In multiple regression analysis, the concentration and FCR of VLDL-apoB-100 (β-coefficient = 0.708 and -0.518, respectively) and IDL-apoB-100 (β-coefficient = 0.354 and -0.447, respectively) were independent predictors of cholesterol efflux. The association of cholesterol efflux with apoB-100 metabolism was diminished after removal of apoB-100-containing lipoproteins from plasma prior to efflux. All associations, except for cholesteryl ester transfer protein, were lost when cholesterol efflux to isolated HDL was tested.
  
  
  CONCLUSIONS
  The plasma concentration and kinetics of apoB-100-containing lipoproteins are significant predictors of the capacity of whole plasma to effect cellular cholesterol efflux.
authors: School of Medicine and Pharmacology, University of Western Australia, Royal Perth Hospital, G.P.O. Box X2213, Perth, Western Australia 6847, Australia.
authors: Dick C
authors: DC
authors: Chan
authors: Anh
authors: A
authors: Hoang
authors: P Hugh R
authors: PH
authors: Barrett
authors: Annett T Y
authors: AT
authors: Wong
authors: Paul J
authors: PJ
authors: Nestel
authors: Dmitri
authors: D
authors: Sviridov
authors: Gerald F
authors: GF
authors: Watts
mesh_terms: D000328:Adult; D000368:Aged; D000886:Anthropometry; D016632:Apolipoprotein A-I / Q000096:biosynthesis; D016633:Apolipoprotein A-II / Q000096:biosynthesis*; D053299:Apolipoprotein B-100 / Q000096:biosynthesis*; D001774:Blood Chemical Analysis; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D012044:Regression Analysis
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D053299:Apolipoprotein B-100; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D002784:Cholesterol