title: Cellular cholesterol efflux and cholesterol loading capacity of serum: effects of LDL-apheresis.
abstract: High LDL-cholesterol (LDL-C) characterizes familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH). LDL-apheresis, used in these patients to reduce LDL-C levels, has been shown to also affect HDL levels and composition. We studied LDL-apheresis effects on six FH and nine FCH subjects' serum capacity to modulate cellular cholesterol efflux, an index of HDL functionality, and to load macrophages with cholesterol. Serum cholesterol efflux capacity (CEC) and macrophage cholesterol loading capacity (CLC) were measured before, immediately after, and two days after LDL-apheresis. The procedure reduced total cholesterol (TC), LDL-C, and apoB plasma levels (-69%, -80% and -74%, respectively), parameters only partially restored two days later. HDL-C and apoA-I plasma levels, reduced after LDL-apheresis (-27% and -16%, respectively), were restored to almost normal levels two days later. LDL-apheresis reduced serum aqueous diffusion (AD) CEC, SR-BI-CEC, and ABCA1-CEC. AD and SR-BI were fully restored whereas ABCA1-CEC remained low two days later. Sera immediately and two days after LDL-apheresis had a lower CLC than pre-LDL-apheresis sera. In conclusion, LDL-apheresis transiently reduces HDL-C levels and serum CEC, but it also reduces also serum capacity to deliver cholesterol to macrophages. Despite a potentially negative effect on HDL levels and composition, LDL-apheresis may counteract foam cells formation.
authors.affiliation: Department of Pharmacological and Biological Sciences and Applied Chemistries, University of Parma, Parma, Italy.
authors.forename: M P
authors.initials: MP
authors.lastname: Adorni
authors.affiliation: Department of Pharmacological and Biological Sciences and Applied Chemistries, University of Parma, Parma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Zimetti
authors.affiliation: Department of Pharmacological and Biological Sciences and Applied Chemistries, CNR Institute of Clinical Physiology, Pisa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Puntoni
authors.affiliation: Department of Pharmacological and Biological Sciences and Applied Chemistries, Dyslipidemias and Atherosclerosis Laboratory, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bigazzi
authors.affiliation: Department of Pharmacological and Biological Sciences and Applied Chemistries, Dyslipidemias and Atherosclerosis Laboratory, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Sbrana
authors.affiliation: Department of Pharmacological and Biological Sciences and Applied Chemistries, CNR Institute of Clinical Physiology, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Minichilli
authors.affiliation: Department of Pharmacological and Biological Sciences and Applied Chemistries, University of Parma, Parma, Italy. Electronic address: fbernini@unipr.it.
authors.forename: F
authors.initials: F
authors.lastname: Bernini
authors.affiliation: Department of Pharmacological and Biological Sciences and Applied Chemistries, University of Parma, Parma, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Ronda
authors.affiliation: Department of Pharmacological and Biological Sciences and Applied Chemistries, University of Parma, Parma, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Favari
authors.affiliation: Department of Pharmacological and Biological Sciences and Applied Chemistries, CNR Institute of Clinical Physiology, Pisa, Italy; Department of Pharmacological and Biological Sciences and Applied Chemistries, Dyslipidemias and Atherosclerosis Laboratory, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Sampietro
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D001692:Biological Transport; D001781:Blood Component Removal; D018955:CD36 Antigens / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood* / Q000378:metabolism*; D004058:Diffusion; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000628:therapy; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014867:Water / Q000378:metabolism
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; D018955:CD36 Antigens; D008078:Cholesterol, LDL; D014867:Water