title: Atheroprotective reverse cholesterol transport pathway is defective in familial hypercholesterolemia.
abstract: OBJECTIVE
  Low high-density lipoprotein (HDL) cholesterol levels are frequently observed in familial hypercholesterolemia (FH) and might be associated with functional alterations of HDL particles that may influence their efficaciousness in the reverse cholesterol transport pathway.
  
  
  RESULTS
  We evaluated key steps of the reverse cholesterol transport, ie, cellular free cholesterol efflux, cholesteryl ester transfer protein-mediated cholesteryl ester (CE) transfer from HDL to apolipoprotein B-containing lipoproteins, and hepatic HDL-CE uptake, in patients displaying FH (n = 12) and in healthy normolipidemic control subjects (n = 12). Large HDL2 particles isolated from FH patients displayed a reduced capacity to mediate free cholesterol efflux via both scavenger receptor-BI- and ABCG1-dependent pathways. A significant inverse relationship between scavenger receptor-BI-dependent HDL2 efflux capacity and carotid intima-media thickness (r = -0.473; P = 0.0186), as well as between ABCG1-dependent HDL2 efflux capacity and carotid intima-media thickness (r = -0.485; P = 0.0212), was detected. We also observed an elevated cholesteryl ester transfer protein-mediated CE transfer from HDL2 and HDL3 particles to low-density lipoprotein and a reduced capacity of HDL particles to deliver CEs to the liver.
  
  
  CONCLUSIONS
  We demonstrated that the centripetal movement of cholesterol from peripheral tissues, including the vessel wall, to feces is defective in FH, thereby emphasizing its atherogenicity.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMRS 939, Hôpital de la Pitié, Paris, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Bellanger
authors.forename: Alexina
authors.initials: A
authors.lastname: Orsoni
authors.forename: Zélie
authors.initials: Z
authors.lastname: Julia
authors.forename: Natalie
authors.initials: N
authors.lastname: Fournier
authors.forename: Eric
authors.initials: E
authors.lastname: Frisdal
authors.forename: Emilie
authors.initials: E
authors.lastname: Duchene
authors.forename: Eric
authors.initials: E
authors.lastname: Bruckert
authors.forename: Alain
authors.initials: A
authors.lastname: Carrie
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnefont-Rousselot
authors.forename: John
authors.initials: J
authors.lastname: Pirault
authors.forename: Flora
authors.initials: F
authors.lastname: Saint-Charles
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesnik
authors.forename: Wilfried
authors.initials: W
authors.lastname: Le Goff
authors.forename: Maryse
authors.initials: M
authors.lastname: Guerin
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; D000293:Adolescent; D000328:Adult; D000818:Animals; D001055:Apolipoproteins B / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D001692:Biological Transport; D016466:CHO Cells; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000378:metabolism; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D006224:Cricetinae; D003412:Cricetulus; D005243:Feces / Q000737:chemistry; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000378:metabolism; D005602:France; D056945:Hep G2 Cells; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D049294:Phospholipid Transfer Proteins / Q000097:blood; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D014162:Transfection; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000378:metabolism; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000378:metabolism; D014463:Ultrasonography; D055815:Young Adult
chemical_list: C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D001055:Apolipoproteins B; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; C493430:PLTP protein, human; D049294:Phospholipid Transfer Proteins; D011973:Receptors, LDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D002784:Cholesterol