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 preβ1-apoA-I-containing lipoproteins (LpA-I)-like particles similar to those of native plasma. Isolated preβ1-LpA-I-like particles inhibited the binding of 125I-apoA-I to ABCA1 more efficiently than HDL3 (IC50 = 2.20 ± 0.35 vs. 37.60 ± 4.78 μg/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 (∼50% and 40%, respectively) in cAMP-stimulated cells compared with unstimulated cells. Similarly, both phospholipid and free cholesterol efflux to either isolated native preβ1-LpA-I and preβ1-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 preβ1-LpA-I nor free cholesterol efflux.These results indicate that DMPC enrichment of normal plasma resulted in the redistribution of apoA-I from α-HDL to preβ-HDL, allowing for more efficient ABCA1-mediated cellular lipid release. Increasing the plasma preβ1-LpA-I level by either pharmacological agents or direct infusions might prevent foam cell formation and reduce atherosclerotic vascular disease.

Keywords

• lipid-poor apolipoprotein A-I
• ATP binding cassette transporter A1
• cholesterol efflux
• high density lipoprotein