出版社：American Society for Biochemistry and Molecular Biology
摘要：It has been suggested that ABCA1 interacts preferentially withlipid-poor apolipoprotein A-I (apoA-I). Here, we show that treatmentof plasma with dimyristoyl phosphatidylcholine (DMPC) multilamellarvesicles generates preß1-apoA-I-containing lipoproteins(LpA-I)-like particles similar to those of native plasma. Isolatedpreß1-LpA-I-like particles inhibited the binding of125I-apoA-I to ABCA1 more efficiently than HDL3 (IC50 = 2.20± 0.35 vs. 37.60 ± 4.78 µg/ml). We nextinvestigated the ability of DMPC-treated plasma to promote phospholipidand unesterified (free) cholesterol efflux from J774 macrophagesstimulated or not with cAMP. At 2 mg DMPC/ml plasma, both phospholipidand free cholesterol efflux were increased (50% and 40%, respectively)in cAMP-stimulated cells compared with unstimulated cells. Similarly,both phospholipid and free cholesterol efflux to either isolatednative preß1-LpA-I and preß1-LpA-I-likeparticles were increased significantly in stimulated cells.Furthermore, glyburide significantly inhibited phospholipidand free cholesterol efflux to DMPC-treated plasma. Removalof apoA-I-containing lipoproteins from normolipidemic plasmadrastically reduced free cholesterol efflux mediated by DMPC-treatedplasma. Finally, treatment of Tangier disease plasma with DMPCaffected the amount of neither preß1-LpA-I nor freecholesterol efflux.
These results indicate that DMPC enrichment of normal plasmaresulted in the redistribution of apoA-I from -HDL to preß-HDL,allowing for more efficient ABCA1-mediated cellular lipid release.Increasing the plasma preß1-LpA-I level by eitherpharmacological agents or direct infusions might prevent foamcell formation and reduce atherosclerotic vascular disease.Abbreviations: apoA-I, apolipoprotein A-I; BBSM, bovine brain sphingomyelin; DMPC, dimyristoyl phosphatidylcholine; MLV, multilamellar vesicle; PEG, polyethylene glycol; POPC, palmitoyloleoyl phosphatidylcholine; preß1-LpA-I, preß1 apoA-I-containing lipoproteins; RCT, reverse cholesterol transport; SR-BI, scavenger receptor class B type I; TD, Tangier disease; 2D-PAGGE, two-dimensional polyacrylamide nondenaturing gradient gel electrophoresis
Supplementary key words lipid-poor apolipoprotein A-I • ATP binding cassette transporter A1 • cholesterol efflux • high density lipoprotein
50% and 40%, respectively) in cAMP-stimulated cells compared with unstimulated cells. Similarly, both phospholipid and free cholesterol efflux to either isolated native preß1-LpA-I and preß1-LpA-I-like particles were increased significantly in stimulated cells. Furthermore, glyburide significantly inhibited phospholipid and free cholesterol efflux to DMPC-treated plasma. Removal of apoA-I-containing lipoproteins from normolipidemic plasma drastically reduced free cholesterol efflux mediated by DMPC-treated plasma. Finally, treatment of Tangier disease plasma with DMPC affected the amount of neither preß1-LpA-I nor free cholesterol efflux.
These results indicate that DMPC enrichment of normal plasma resulted in the redistribution of apoA-I from 
-HDL to preß-HDL, allowing for more efficient ABCA1-mediated cellular lipid release. Increasing the plasma preß1-LpA-I level by either pharmacological agents or direct infusions might prevent foam cell formation and reduce atherosclerotic vascular disease.
Abbreviations: apoA-I, apolipoprotein A-I; BBSM, bovine brain sphingomyelin; DMPC, dimyristoyl phosphatidylcholine; MLV, multilamellar vesicle; PEG, polyethylene glycol; POPC, palmitoyloleoyl phosphatidylcholine; preß1-LpA-I, preß1 apoA-I-containing lipoproteins; RCT, reverse cholesterol transport; SR-BI, scavenger receptor class B type I; TD, Tangier disease; 2D-PAGGE, two-dimensional polyacrylamide nondenaturing gradient gel electrophoresis
Supplementary key words lipid-poor apolipoprotein A-I • ATP binding cassette transporter A1 • cholesterol efflux • high density lipoprotein
