title: LDL-apheresis depletes apoE-HDL and pre-β1-HDL in familial hypercholesterolemia: relevance to atheroprotection.
abstract: Subnormal HDL-cholesterol (HDL-C) and apolipoprotein (apo)AI levels are characteristic of familial hypercholesterolemia (FH), reflecting perturbed intravascular metabolism with compositional anomalies in HDL particles, including apoE enrichment. Does LDL-apheresis, which reduces HDL-cholesterol, apoAI, and apoE by adsorption, induce selective changes in HDL subpopulations, with relevance to atheroprotection? Five HDL subpopulations were fractionated from pre- and post-LDL-apheresis plasmas of normotriglyceridemic FH subjects (n = 11) on regular LDL-apheresis (>2 years). Apheresis lowered both plasma apoE (-62%) and apoAI (-16%) levels, with preferential, genotype-independent reduction in apoE. The mass ratio of HDL2:HDL3 was lowered from ~1:1 to 0.72:1 by apheresis, reflecting selective removal of HDL2 mass (80% of total HDL adsorbed). Pre-LDL-apheresis, HDL2 subpopulations were markedly enriched in apoE, consistent with ~1 copy of apoE per 4 HDL particles. Large amounts (50-66%) of apoE-HDL were removed by apheresis, preferentially in the HDL2b subfraction (-50%); minor absolute amounts of apoE-HDL were removed from HDL3 subfractions. Furthermore, pre-β1-HDL particle levels were subnormal following removal (-53%) upon apheresis, suggesting that cellular cholesterol efflux may be defective in the immediate postapheresis period. In LDL-receptor (LDL-R) deficiency, LDL-apheresis may enhance flux through the reverse cholesterol transport pathway and equally attenuate potential biglycan-mediated deposition of apoE-HDL in the arterial matrix.
authors.affiliation: INSERM UMR-S939, Hôpital de la Pitié-Salpetriere, Paris, France; Université Pierre et Marie Curie-Paris 6, Hôpital de la Pitié-Salpetriere, Paris, France.
authors.forename: Alexina
authors.initials: A
authors.lastname: Orsoni
authors.affiliation: Haemobiotherapy Unit, AP-HP, Hôpital de la Pitié-Salpetriere, Paris, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Saheb
authors.affiliation: Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Johannes H M
authors.initials: JHM
authors.lastname: Levels
authors.affiliation: Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Geesje
authors.initials: G
authors.lastname: Dallinga-Thie
authors.affiliation: Haemobiotherapy Unit, AP-HP, Hôpital de la Pitié-Salpetriere, Paris, France.
authors.forename: Marielle
authors.initials: M
authors.lastname: Atassi
authors.affiliation: Metabolic Biochemistry, AP-HP, Hôpital de la Pitié-Salpetriere, Paris, France.
authors.forename: Randa
authors.initials: R
authors.lastname: Bittar
authors.affiliation: INSERM UMR-S939, Hôpital de la Pitié-Salpetriere, Paris, France; Université Pierre et Marie Curie-Paris 6, Hôpital de la Pitié-Salpetriere, Paris, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Robillard
authors.affiliation: Endocrinology-Metabolism Service, AP-HP, Hôpital de la Pitié-Salpetriere, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bruckert
authors.affiliation: INSERM UMR-S939, Hôpital de la Pitié-Salpetriere, Paris, France; Université Pierre et Marie Curie-Paris 6, Hôpital de la Pitié-Salpetriere, Paris, France.
authors.forename: Anatol
authors.initials: A
authors.lastname: Kontush
authors.affiliation: INSERM UMR-S939, Hôpital de la Pitié-Salpetriere, Paris, France; Université Pierre et Marie Curie-Paris 6, Hôpital de la Pitié-Salpetriere, Paris, France; Molecular and Oncologic Endocrinology, AP-HP, Hôpital de la Pitié-Salpetriere, Paris, France; and.
authors.forename: Alain
authors.initials: A
authors.lastname: Carrié
authors.affiliation: INSERM UMR-S939, Hôpital de la Pitié-Salpetriere, Paris, France; Université Pierre et Marie Curie-Paris 6, Hôpital de la Pitié-Salpetriere, Paris, France. Electronic address: john.chapman@upmc.fr.
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
mesh_terms: D000327:Adsorption; D000328:Adult; D001057:Apolipoproteins E / Q000097:blood*; D050197:Atherosclerosis / Q000150:complications / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D001781:Blood Component Removal; D016022:Case-Control Studies; D005260:Female; D053442:High-Density Lipoproteins, Pre-beta / Q000097:blood* / Q000737:chemistry; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D007249:Inflammation / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008297:Male; D020543:Proteome / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency; D012189:Retrospective Studies
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D053442:High-Density Lipoproteins, Pre-beta; D008077:Lipoproteins, LDL; D020543:Proteome; D011973:Receptors, LDL