title: Serum, but not monocyte macrophage foam cells derived from low HDL-C subjects, displays reduced cholesterol efflux capacity.
abstract: The main antiatherogenic function of HDL is to promote the efflux of cholesterol from peripheral cells and transport it to the liver for excretion in a process termed reverse cholesterol transport. The aim of this study was to evaluate the cholesterol efflux capacity in low- and high-HDL subjects by utilizing monocytes and serum from 18 low-HDL and 15 high-HDL subjects. Low and high HDL levels were defined, respectively, as HDL < or =10(th) and HDL > or =90(th) Finnish age/sex-specific percentile. Cholesterol efflux from [(3)H]cholesterol-oleate-acetyl-LDL-loaded monocyte-derived macrophages to standard apolipoprotein A-I (apoA-I), HDL(2), and serum was measured. In addition, cholesterol efflux from acetyl-LDL-loaded human THP-1 macrophages to individual sera (0.5%) derived from the study subjects was evaluated. Cholesterol efflux to apoA-I, HDL(2), and serum from macrophage foam cells derived from low- and high-HDL subjects was similar. The relative ABCA1 and ABCG1 mRNA expression levels in unloaded macrophages, as well as their protein levels in loaded macrophage foam cells, were similar in the two study groups. Cholesterol efflux from THP-1 foam cells to serum recovered from high-HDL subjects was slightly higher than that to serum from low-HDL subjects (P = 0.046). Cholesterol efflux from THP-1 macrophages to serum from study subjects correlated with serum apoB (P = 0.033), apoA-I (P = 0.004), apoA-II (P < 0.0001), and the percentage of apoA-I present in the form of prebeta-HDL (P = 0.0001). Our data reveal that macrophages isolated from either low- or high-HDL subjects display similar cholesterol efflux capacity to exogenous acceptors. However, sera from low-HDL subjects have poorer cholesterol acceptor ability as compared with sera from high-HDL subjects.
authors.affiliation: Division of Cardiology, Department of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nakanishi
authors.forename: Riikka
authors.initials: R
authors.lastname: Vikstedt
authors.forename: Sanni
authors.initials: S
authors.lastname: Söderlund
authors.forename: Miriam
authors.initials: M
authors.lastname: Lee-Rueckert
authors.forename: Anne
authors.initials: A
authors.lastname: Hiukka
authors.forename: Christian
authors.initials: C
authors.lastname: Ehnholm
authors.forename: Mikko
authors.initials: M
authors.lastname: Muilu
authors.forename: Jari
authors.initials: J
authors.lastname: Metso
authors.forename: Jussi
authors.initials: J
authors.lastname: Naukkarinen
authors.forename: Leena
authors.initials: L
authors.lastname: Palotie
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
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; D000328:Adult; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D005487:Foam Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / 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; D008076:Cholesterol, HDL; D012333:RNA, Messenger; D002784:Cholesterol