Enhanced removal of cholesterol from macrophage foam cells to serum from type IV hypertriglyceridemic subjects.
Hypertriglyceridemia being an independent cardiovascular risk factor, we have compared the potential of sera from asymptomatic hypertriglyceridemic (HTG) type IIb, type IV or normolipidemic (NLP) subjects to promote both fractional cholesterol efflux and cellular cholesterol mass changes using macrophage foam cells. The J774 cells loaded with cholesterol by incubation with acetylated LDL were incubated in the absence or presence of cAMP to upregulate ABCA1 (ATP binding cassette transporter A1) and then incubated for 24h with 1% serum. Compared with NLP, type IV sera exhibited a major increase in ABCA1-dependent efflux while type IIb sera exhibited a moderate but not significant increased ABCA1-mediated efflux. Moreover, positive correlations were established between ABCA1-dependent efflux and the serum prebeta-HDL or TG concentrations. The major finding was that the sera from type IV induced higher total cholesterol and cholesteryl ester mass depletions from ABCA1-expressing cells compared with other groups. Moreover, negative correlations were obtained between total cholesterol or cholesteryl ester mass changes and serum prebeta-HDL levels. In conclusion, we demonstrated for the first time that the serum prebeta-HDL present in high proportions in type IV HTG subjects are not only responsible for higher cholesterol efflux potential but also for increased abilities to promote net removal of cholesterol from macrophage foam cells.
Attia
Nesrine
N
Univ Paris-Sud, UMR INRA 1154, UFR de Pharmacie, 92296 Châtenay-Malabry, France.
Ramaharo
Angela
A
Paul
Jean-Louis
JL
Cambillau
Michèle
M
Beaune
Philippe
P
Grynberg
Alain
A
Simon
Alain
A
Fournier
Natalie
N
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000328:Adult; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005487:Foam Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000276:immunology* / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008875:Middle Aged; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014316:Tritium
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; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D014280:Triglycerides; C032629:acetyl-LDL; D014316:Tritium