title: Structural modification of plasma HDL by phospholipids promotes efficient ABCA1-mediated cholesterol release.
abstract: It has been suggested that ABCA1 interacts preferentially with lipid-poor apolipoprotein A-I (apoA-I). Here, we show that treatment of plasma with dimyristoyl phosphatidylcholine (DMPC) multilamellar vesicles generates prebeta(1)-apoA-I-containing lipoproteins (LpA-I)-like particles similar to those of native plasma. Isolated prebeta(1)-LpA-I-like particles inhibited the binding of (125)I-apoA-I to ABCA1 more efficiently than HDL(3) (IC(50) = 2.20 +/- 0.35 vs. 37.60 +/- 4.78 microg/ml). We next investigated the ability of DMPC-treated plasma to promote phospholipid and unesterified (free) cholesterol efflux from J774 macrophages stimulated or not with cAMP. At 2 mg DMPC/ml plasma, both phospholipid and free cholesterol efflux were increased ( approximately 50% and 40%, respectively) in cAMP-stimulated cells compared with unstimulated cells. Similarly, both phospholipid and free cholesterol efflux to either isolated native prebeta(1)-LpA-I and prebeta(1)-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 prebeta(1)-LpA-I nor free cholesterol efflux. These results indicate that DMPC enrichment of normal plasma resulted in the redistribution of apoA-I from alpha-HDL to prebeta-HDL, allowing for more efficient ABCA1-mediated cellular lipid release. Increasing the plasma prebeta(1)-LpA-I level by either pharmacological agents or direct infusions might prevent foam cell formation and reduce atherosclerotic vascular disease.
authors.affiliation: Cardiovascular Genetics Laboratory, Cardiology Division, McGill University Health Center/Royal Victoria Hospital, Montréal, Québec H3A 1A1, Canada.
authors.forename: Houssein
authors.initials: H
authors.lastname: Hajj Hassan
authors.forename: Sacha
authors.initials: S
authors.lastname: Blain
authors.forename: Betsie
authors.initials: B
authors.lastname: Boucher
authors.forename: Maxime
authors.initials: M
authors.lastname: Denis
authors.forename: Larbi
authors.initials: L
authors.lastname: Krimbou
authors.forename: Jacques
authors.initials: J
authors.lastname: Genest
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood* / Q000737:chemistry*; D053440:Lipoproteins, HDL3; D008081:Liposomes / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010743:Phospholipids / Q000737:chemistry*; D013631:Tangier Disease / Q000097:blood
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D008081:Liposomes; D010743:Phospholipids; D002784:Cholesterol; D004134:Dimyristoylphosphatidylcholine