title: Cholesterol efflux from J774 macrophages and Fu5AH hepatoma cells to serum is preserved in CETP-deficient patients.
abstract: BACKGROUND
  The role of CETP in the development of atherosclerosis is debatable, and few data exist regarding the total impact of CETP inhibition on cholesterol efflux.
  
  
  METHODS
  Acceptor capacities of whole serum and HDL subfractions separated by HPLC were compared using 2 different cell systems. Subjects with CETP deficiency (2 homozygous, 1 compound heterozygous, and 5 heterozygous) were analyzed along with 10 normolipidemic controls. The fractional efflux from cholesterol-labeled Fu5AH hepatoma cells was determined to be SR-BI mediated. The efflux difference between control and liver X receptor (LXR) agonist-induced ABCA1-upregulated J774 macrophages was considered as a measure of ABCA1-mediated efflux.
  
  
  RESULTS
  For the Fu5AH cell system, the total acceptor capacities of whole serum and HPLC-separated HDL fraction 2 obtained from the homozygous subjects were 38% and 116% higher than the corresponding values for the controls, respectively (p<0.05). For the J774 cell system, the total acceptor capacities of whole serum and HPLC-separated HDL fractions were similar among the CETP-deficient subjects and controls.
  
  
  CONCLUSIONS
  Serum from homozygous subjects with CETP-null defects exhibited enhanced acceptor capacity via an SR-BI dependent pathway, which is regulated by the middle HPLC-separated HDL fraction. Further, the cholesterol acceptor capacity of serum obtained from patients having complete and partial CETP deficiency was preserved via an ABCA1-dependent pathway.
authors.affiliation: Department of Internal Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan. miwakc2004@yahoo.co.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Miwa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Inazu
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kawashiri
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nohara
authors.forename: Toshinori
authors.initials: T
authors.lastname: Higashikata
authors.forename: Junji
authors.initials: J
authors.lastname: Kobayashi
authors.forename: Junji
authors.initials: J
authors.lastname: Koizumi
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Nakajima
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Nakano
authors.forename: Manabu
authors.initials: M
authors.lastname: Niimi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mabuchi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamagishi
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D045744:Cell Line, Tumor; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics / Q000502:physiology*; D008076:Cholesterol, HDL / Q000097:blood* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D000071518:Liver X Receptors; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D057093:Orphan Nuclear Receptors; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D014280:Triglycerides