期刊
JOURNAL OF LIPID RESEARCH
卷 46, 期 7, 页码 1457-1465出版社
ELSEVIER
DOI: 10.1194/jlr.M400477-JLR200
关键词
lipid-poor apolipoprotein A-I; ATP binding cassette transporter A1; cholesterol efflux; high density lipoprotein
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 pre beta(1)-apoA-I-containing lipoproteins (LpA-I)-like particles similar to those of native plasma. Isolated pre beta(1)-LpA-I-like particles inhibited the binding of I-125- apoA-I to ABCA1 more efficiently than HDL3 (IC50 = 2.20 +/- 0.35 vs. 37.60 +/- 4.78 mu g/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 (similar to 50% and 40%, respectively) in cAMP-stimulated cells compared with unstimulated cells. Similarly, both phospholipid and free cholesterol efflux to either isolated native pre beta(1)-LpA-I and pre beta(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 pre beta(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 pre beta-HDL, allowing for more efficient ABCA1-mediated cellular lipid release. Increasing the plasma pre beta(1)-LpA-I level by either pharmacological agents or direct infusions might prevent foam cell formation and reduce atherosclerotic vascular disease. Hajj Hassan, H., S. Blain, B. Boucher, M. Denis, L. Krimbou, and J. Genest. Structural modification of plasma HDL by phospholipids promotes efficient ABCA1-mediated cholesterol release.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据