FORMATION OF NEW HDL PARTICLES FROM LIPID-FREE APOLIPOPROTEIN-A-I

Remodelling of plasma high density lipoproteins (HDL) promotes the dis sociation of lipid-free apolipoprotein (apo)A-I from the particles. In the present study, we have investigated the formation of new HDL part icles from lipid-free apoA-I in a process dependent on the presence of non-esterified fatty acids (NEFA) and other lipoprotein fractions (as donors of lipid). Incubations were carried out that included lipid-fr ee apoA-I, VLDL, and lipoprotein lipase (LPL) or lipid-free apoA-I, ei ther VLDL or LDL, and sodium oleate. Any new HDL particles that were f ormed were separated from lipid-free apoA-I in the ultracentrifuge. Wh en any one of the ingredients in the incubation was absent, the apoA-I remained lipid-free; however, when all the ingredients were present, a significant proportion of the apoA-I was recovered in the HDL densit y fraction. This coincided with the formation of at least three HDL-si zed subpopulations; one of the subpopulations was considerably smaller than HDL(3c) and had pre-beta 1 mobility while two were in the size r ange of human HDL(2b) and HDL(3c) and had pre-beta 2 electrophoretic m obility. The new HDL were predominantly discoidal in shape and their m ajor constituents were apoA-I, phospholipid, and unesterified choleste rol. In conclusion, these results show that lipid-free apoA-I can form new HDL particles in the presence of NEFA and other lipoprotein fract ions. The formation of pre-beta 1 HDL from lipid-free apoA-I indicates that this process is potentially of great importance in terms of gene rating plasma accepters of cell cholesterol in reverse cholesterol tra nsport.