No abstract

HDL is believed to be a potent physiological protective system against atherosclerotic vascular disease. Although it has become generally accepted that this protective effect of HDL is attributable to its pivotal role in the reverse cholesterol transport (RCT) process (1, 2), structural determinants of molecular interactions between circulating HDL particles and key cell proteins governing the RCT process are complex and not well understood.A growing body of evidence indicates that ABCA1 is a critical cell surface protein required for the transfer of cellular lipid and the maintenance of HDL levels in plasma and is likely important for the first step of RCT from peripheral tissues, including macrophages in the vessel wall (3, 4). Furthermore, Brewer and colleagues (5) have documented that hepatic ABCA1 is a key protein for the formation and maintenance of plasma HDL levels. Moreover, the importance of ABCA1 in the lipidation of apolipoprotein A-I (apoA-I) is highlighted by the finding that Ͼ 50 mutations in the ABCA1 gene have been associated with a variety of clinically distinct HDL deficiency diseases, including Tangier disease (TD) and familial HDL deficiency (6, 7). These patients are characterized by extremely low HDL-cholesterol levels, caused by defective transport of cellular cholesterol and phospholipids to the extracellular space, leading to hypercatabolism of lipidpoor nascent HDL particles (8).Earlier studies by Fielding and colleagues (9, 10) have documented that a minor subspecies of human HDL that migrates with pre ␤ mobility on agarose gels can remove free cholesterol from cultured fibroblasts at a faster rate than ␣ -migrating HDL, which constitutes the bulk of plasma HDL. Furthermore, it was documented that pre ␤ -HDL particles were present in the peripheral lymph of dogs (11), suggesting a key role for these particles in the Abbreviations: apoA-I, apolipoprotein A-I; BBSM, bovine brain sphingomyelin; DMPC, dimyristoyl phosphatidylcholine; MLV, multilamellar vesicle; PEG, polyethylene glycol; POPC, palmitoyloleoyl phosphatidylcholine; pre ␤ 1 -LpA-I, pre ␤ 1 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.