title: Reconstituted high density lipoprotein reduces the capacity of oxidatively modified low density lipoprotein to accumulate cholesteryl esters in mouse peritoneal macrophages.
abstract: Oxidized low density lipoprotein (ox-LDL) was incubated with discoidal complexes of apolipoprotein A-I (apo A-I) and dimyristoylphosphatidylcholine (DMPC) (DMPC/apo A-I) in a cell-free system and re-isolated on Sephacryl S-400 gel filtration chromatography. Analyses of re-isolated ox-LDL showed that apo A-I was transferred from DMPC/apo A-I to ox-LDL, which accounted for 10% of the total protein of ox-LDL. Re-isolated ox-LDL also showed a 2.2-fold increase in phospholipid and a 14% decrease in cholesterol content on an apo B basis. The electrophoretic mobility of re-isolated ox-LDL was markedly reduced almost to that of native LDL. Moreover, the amounts of re-isolated ox-LDL to be degraded by mouse peritoneal macrophages as well as the capacity of re-isolated ox-LDL to accumulate cholesteryl esters (CE) in these cells were markedly reduced (60% and 80% reduction, respectively), suggesting that the ligand activity of ox-LDL for the scavenger receptor was significantly reduced upon treatment with DMPC/apo A-I. Parallel incubation of ox-LDL with free apo A-I led to a similar incorporation of apo A-I into ox-LDL. However, it had no effects on the ligand activity of ox-LDL. Thus, it is likely that the reduction in the ligand activity of ox-LDL by DMPC/apo A-I is explained by the change in the lipid moiety (mainly phospholipid) of ox-LDL. Since discoidal high density lipoprotein (HDL) is known to occur in vivo, this phenomenon might explain one of the anti-atherogenic functions of HDL.
authors.affiliation: Department of Biochemistry, Kumamoto University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sakai
authors.forename: A
authors.initials: A
authors.lastname: Miyazaki
authors.forename: H
authors.initials: H
authors.lastname: Hakamata
authors.forename: Y
authors.initials: Y
authors.lastname: Suginohara
authors.forename: Y I
authors.initials: YI
authors.lastname: Sakamoto
authors.forename: W
authors.initials: W
authors.lastname: Morikawa
authors.forename: S
authors.initials: S
authors.lastname: Kobori
authors.forename: M
authors.initials: M
authors.lastname: Schichiri
authors.forename: S
authors.initials: S
authors.lastname: Horiuchi
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D002474:Cell-Free System; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002788:Cholesterol Esters / Q000378:metabolism*; D002850:Chromatography, Gel; D004134:Dimyristoylphosphatidylcholine / Q000378:metabolism; D004705:Endocytosis; D005487:Foam Cells / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology* / Q000502:physiology; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D010084:Oxidation-Reduction; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
chemical_list: D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D008081:Liposomes; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D004134:Dimyristoylphosphatidylcholine