title: Apolipoprotein AIMilano. Disulfide-linked dimers increase high density lipoprotein stability and hinder particle interconversion in carrier plasma.
abstract: The in vitro metabolism of high density lipoproteins (HDL) in carriers of the apolipoprotein AIMilano (apoAIM) mutant was investigated during incubation of whole plasma and isolated lipoprotein fractions. A reduced cholesterol esterification (16.5 versus 25.0% for controls) and a decreased exchange of lipids between HDL and lower density lipoproteins was observed during incubation (6 h at 37 degrees C) of AIM plasma. Control HDL3 were converted to larger, faster-floating HDL particles, whereas only a fraction of AIM HDL3 followed the same pathway. Incubations were also carried out by mixing HDL3 from controls and AIM carriers with a lipoprotein-depleted plasma fraction in the presence of triglyceride-rich particles isolated from Intralipid. AIM HDL3 again showed a reduced capacity for lipid exchange; some HDL3 particles followed a "normal" conversion to faster-floating, larger HDL, whereas the small AIM HDL3 were not modified, indicating that AIM HDL3 are a mixture of metabolically functional and nonfunctional particles. Following transformation of the apoAIM homo- and heterodimers into their normal counterparts, i.e. monomeric apoAI and -AII, by reduction and carboxamidomethylation of AIM HDL3, the modified HDL3 behave like control HDL3 during incubation with lipoprotein-depleted plasma and triglyceride-rich particles. The presence of AIM dimers is most likely responsible for the increased HDL3 stability in the AIM carriers, indicating that apolipoprotein composition plays a major role in HDL particle interconversion.
authors.affiliation: Center E. Grossi Paoletti, Institute of Pharmacological Sciences, University of Milano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Franceschini
authors.forename: L
authors.initials: L
authors.lastname: Calabresi
authors.forename: C
authors.initials: C
authors.lastname: Tosi
authors.forename: G
authors.initials: G
authors.lastname: Gianfranceschi
authors.forename: C R
authors.initials: CR
authors.lastname: Sirtori
authors.forename: A V
authors.initials: AV
authors.lastname: Nichols
mesh_terms: D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D004220:Disulfides; D006579:Heterozygote; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D009154:Mutation; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D002352:Carrier Proteins; D002788:Cholesterol Esters; D004220:Disulfides; D008075:Lipoproteins, HDL; D014280:Triglycerides; C030363:lipid transfer protein; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase