Acetylated low density lipoprotein reduces its ligand activity for the scavenger receptor after interaction with reconstituted high density lipoprotein.

Complexes of apolipoprotein A-I (apoA-I) with phospholipids are known to induce cholesterol efflux from cells. In a cholesteryl ester accumulation system in which rat peritoneal macrophages were incubated with acetylated low density lipoprotein (acetyl-LDL) and either dimyristoylphosphatidylcholine complexes (DMPC/apoA-I) or native high density lipoprotein (HDL), DMPC/apoA-I exhibited a much stronger effect than native HDL in preventing cholesteryl ester accumulation. The mechanism for this phenomenon was investigated in the present study. After 18 h incubation with DMPC/apoA-I in a cell-free system, acetyl-LDL was re-isolated from DMPC/apoA-I by Sephacryl S-300 gel filtration chromatography. Re-isolated acetyl-LDL exhibited an increase in its phospholipid content by 86% as well as a reduction in the electrophoretic mobility. Its endocytic degradation by macrophages was reduced by 60% when compared with control acetyl-LDL, suggesting a significant reduction in the ligand activity for the macrophage scavenger receptor. Transfer of apolipoproteins between acetyl-LDL and DMPC/apoA-I did not occur. These results indicate that transfer of DMPC from DMPC/apoA-I to acetyl-LDL weakens the ligand activity for the scavenger receptor due probably to a decrease in net negative charge. This study demonstrated for the first time that lipid modification (change in the lipid moiety) of acetyl-LDL can induce alteration in its apolipoprotein moiety, leading to a significant loss of its biological activity. Because discoidal HDLs are known to occur in vivo, this phenomenon may explain one of the anti-atherogenic functions of HDL in vivo.