Apolipoprotein AIMilano. Disulfide-linked dimers increase high density lipoprotein stability and hinder particle interconversion in carrier plasma.
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.
Franceschini
G
G
Center E. Grossi Paoletti, Institute of Pharmacological Sciences, University of Milano, Italy.
Calabresi
L
L
Tosi
C
C
Gianfranceschi
G
G
Sirtori
C R
CR
Nichols
A V
AV
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
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