title: Mechanism of cholesterol efflux in humans after infusion of reconstituted high-density lipoprotein.
abstract: OBJECTIVE
  Infusion of reconstituted HDL (rHDL) leads to changes in HDL metabolism as well as to an increased capacity of plasma to support cholesterol efflux providing an opportunity to investigate mechanisms linking cholesterol efflux to changes in plasma HDL.
  
  
  RESULTS
  Patient plasmas after infusion of rHDL were tested ex vivo for their capacity to stimulate cholesterol efflux. Reconstituted HDL enhanced mobilization of cholesterol from tissues in vivo as shown by rising HDL cholesterol concentrations over the infusion period. Infusion of rHDL in vivo led to increased cholesterol efflux ex vivo; surprisingly, removing apoB-containing lipoproteins while preserving all HDL subfractions eliminated this increase. Infusion of rHDL led to the remodelling of plasma HDL; however, the capacity of plasma to support cholesterol efflux did not correlate with changes in the concentrations of any of HDL subfractions. Unmodified rHDL accounted for only a proportion of the increment in cholesterol efflux capacity. Furthermore, studies using HeLa and BHK cells overexpressing ABCA1, ABCG1, and SR-B1 showed that the contribution of these cellular mediators of cholesterol efflux to the enhanced capacity of plasma for the efflux was minimal.
  
  
  CONCLUSIONS
  Enhanced cholesterol efflux from tissues requires the presence of apoB-containing lipoproteins and may involve enhanced flow of cholesterol through multiple components of the reverse cholesterol transport pathway rather than being determined by a specific HDL subfraction.
authors.affiliation: Baker Heart and Diabetes Institute, PO Box 6492, St. Kilda Rd Central, Melbourne, VIC 8008,  Australia.
authors.forename: Anh
authors.initials: A
authors.lastname: Hoang
authors.forename: Brian G
authors.initials: BG
authors.lastname: Drew
authors.forename: Hann
authors.initials: H
authors.lastname: Low
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
authors.forename: Paul
authors.initials: P
authors.lastname: Nestel
authors.forename: Bronwyn A
authors.initials: BA
authors.lastname: Kingwell
authors.forename: Dmitri
authors.initials: D
authors.lastname: Sviridov
mesh_terms: D000704:Analysis of Variance; D016632:Apolipoprotein A-I / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism / Q000502:physiology*; D001692:Biological Transport / Q000502:physiology; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2; D006801:Humans; D007262:Infusions, Intravenous; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008297:Male; D010949:Plasma / Q000378:metabolism / Q000502:physiology; D016032:Randomized Controlled Trials as Topic; D014316:Tritium
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D014316:Tritium