REMODELING OF RECONSTITUTED HIGH-DENSITY-LIPOPROTEINS BY LECITHIN-CHOLESTEROL ACYLTRANSFERASE

Discoidal reconstituted high density lipoproteins (rHDL) with a diamet er of 7.9 nm, a molar ratio of egg phosphatidylcholine (PC): unesterif ied cholesterol (UC): cholesteryl esters (CE): apolipoprotein (ape) A- I of 33:7:0:1 and containing two molecules of apoA-I per particle were incubated with lecithin:cholesterol acyltransferase (LCAT) in the pre sence of low density Iipoproteins as a source of additional UC and PC for the LCAT reaction. After 24 h of incubation, the rHDL had a diamet er of 8.8 nm, a molar ratio of PC:UC:CE:apoA-I of 16:3:23:1 and contai ned three rattler than two molecules of apoA-I per particle. The fact that there was no change in tile concentration of rHDL-associated apoA -I indicated thar the increase from two to three molecules of apoA-I p er particle was achieved at tile expense of a one-third reduction in t he number of rHDL particles in a process that must have involved parti cle fusion. When the incubations were repeated in the presence of exog enous, lipid-free apoA-I, the resulting rHDL were identical in size an d composition to those generated in its absence. Under these condition s, however, the increase from two to three molecules of apoA-I per rHD L particle coincided with a 50% increase in the concentration of rHDL- associated apoA-I Thus, when lipid-free apoA-I is available, tile LCAT -mediated increase in number of apoA-I molecules per rHDL particle is achieved by a direct incorporation of lipid-free apolipoprotein withou t any need For particle fusion and therefore without a reduction in th e number of rHDL particles.