title: Impact of LDL apheresis on atheroprotective reverse cholesterol transport pathway in familial hypercholesterolemia.
abstract: In familial hypercholesterolemia (FH), low HDL cholesterol (HDL-C) levels are associated with functional alterations of HDL particles that reduce their capacity to mediate the reverse cholesterol transport (RCT) pathway. The objective of this study was to evaluate the consequences of LDL apheresis on the efficacy of the RCT pathway in FH patients. LDL apheresis markedly reduced abnormal accelerated cholesteryl ester transfer protein (CETP)-mediated cholesteryl ester (CE) transfer from HDL to LDL, thus reducing their CE content. Equally, we observed a major decrease (-53%; P < 0.0001) in pre-β1-HDL levels. The capacity of whole plasma to mediate free cholesterol efflux from human macrophages was reduced (-15%; P < 0.02) following LDL apheresis. Such reduction resulted from a marked decrease in the ABCA1-dependent efflux (-71%; P < 0.0001) in the scavenger receptor class B type I-dependent efflux (-21%; P < 0.0001) and in the ABCG1-dependent pathway (-15%; P < 0.04). However, HDL particles isolated from FH patients before and after LDL apheresis displayed a similar capacity to mediate cellular free cholesterol efflux or to deliver CE to hepatic cells. We demonstrate that rapid removal of circulating lipoprotein particles by LDL apheresis transitorily reduces RCT. However, LDL apheresis is without impact on the intrinsic ability of HDL particles to promote either cellular free cholesterol efflux from macrophages or to deliver CE to hepatic cells.
authors.affiliation: INSERM UMRS939,  Hôpital de la Pitié, Paris,  France.
authors.forename: Alexina
authors.initials: A
authors.lastname: Orsoni
authors.forename: Elise F
authors.initials: EF
authors.lastname: Villard
authors.forename: Eric
authors.initials: E
authors.lastname: Bruckert
authors.forename: Paul
authors.initials: P
authors.lastname: Robillard
authors.forename: Alain
authors.initials: A
authors.lastname: Carrie
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnefont-Rousselot
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.forename: Geesje M
authors.initials: GM
authors.lastname: Dallinga-Thie
authors.forename: Wilfried
authors.initials: W
authors.lastname: Le Goff
authors.forename: Maryse
authors.initials: M
authors.lastname: Guerin
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D001781:Blood Component Removal / Q000379:methods*; D016466:CHO Cells; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000302:isolation & purification*; D006224:Cricetinae; D004951:Esterification; D005260:Female; D053442:High-Density Lipoproteins, Pre-beta / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C419353:ABCG1 protein, human; 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; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D053442:High-Density Lipoproteins, Pre-beta; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B