title: Cholesterol efflux mediators in homozygous familial hypercholesterolemia patients on low-density lipoprotein apheresis.
abstract: BACKGROUND
  Homozygous familial hypercholesterolemia (FH) is a rare disorder that may affect 1 person per million. Early initiation of aggressive cholesterol-lowering therapy is essential to prevent premature coronary heart disease. Selective removal of low-density lipoprotein (LDL) by LDL apheresis is a reliable method of treatment.
  
  
  RESULTS
  Cholesterol efflux mediators of homozygous FH patients on weekly LDL apheresis were compared with those of age- and sex-matched heterozygous FH patients receiving oral medication only and with healthy control subjects. The data show that (1) compared with healthy controls, homozygous FH patients have significantly lower plasma levels of high-density lipoprotein cholesterol and apoA-I and significantly lower cholesterol-acceptor capacity of serum to promote cholesterol efflux from cholesterol-loaded THP-1 cells, combined with significantly lower peripheral blood mononuclear cell gene expression levels of ATP-binding cassette (ABC) transporter G1 and borderline-significantly lower levels of ABCA1 and scavenger receptor class B type I (SR-BI); and (2) compared with pre-LDL apheresis (a day before treatment), postapheresis (15 days later; on the day after the weekly treatment) levels of HDL cholesterol and apoA-I were significantly reduced, with no significant effect on cholesterol-acceptor capacity of serum or on peripheral blood mononuclear cell gene expression levels of the cellular transporters, except for a borderline-significant reduction in ABCA1 mRNA levels.
  
  
  CONCLUSIONS
  The data showing decreased levels of cholesterol efflux mediators in plasma and cells may suggest that the overall cholesterol efflux capacity is impaired in homozygous FH patients. However, LDL apheresis may maintain cholesterol efflux capacity, despite a lowering levels of high-density lipoprotein cholesterol and apoA-I.
authors: Lipid Clinic, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors: Marit S
authors: MS
authors: Nenseter
authors: Ingunn
authors: I
authors: Narverud
authors: Asgeir
authors: A
authors: Græsdal
authors: Martin P
authors: MP
authors: Bogsrud
authors: Pål
authors: P
authors: Aukrust
authors: Kjetil
authors: K
authors: Retterstøl
authors: Leiv
authors: L
authors: Ose
authors: Bente
authors: B
authors: Halvorsen
authors: Kirsten B
authors: KB
authors: Holven
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D001781:Blood Component Removal; D002460:Cell Line; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B