Enhanced metabolism of normolipidemic human plasma very low density lipoprotein in cultured cells by exogenous apolipoprotein E-3.

In this investigation in cultured human fibroblasts, an attempt was made to determine the optimal metabolism of apolipoprotein (apo) B-100 lipoproteins from normolipidemic human subjects. We supplemented culture systems containing 125I-lipoproteins with exogenous recombinant or plasmatic apo E-3. Very low density lipoprotein (VLDL) fractions I, II, and III, and low density lipoproteins (LDL) were prepared from one E 4/3 and four E 3/3 subjects. Without added apo E-3, cellular metabolism (binding, cell association, and degradation) of VLDL-I, II, and III was negligible. Exogenous apo E-3 caused a many-fold enhancement of the metabolism of the three VLDL fractions, but LDL was not affected. The effects of apo E-3 were specific, not observed with apo E-2, and not observed on receptor-negative cells. Exogenous apo E-3 also enhanced down-regulation of cellular sterol synthesis by the VLDLs, but not LDL, indicating increased particle catabolism by the cells. The optimal concentrations of exogenous apo E-3 were 4 to 6 micrograms protein/15 micrograms VLDL-protein, when most of the added apo E-3 became associated with the VLDL particles. Apo E-3 failed to associate with LDL. These results demonstrate that availability and association of adequate amounts of apo E-3 are crucial for optimal cellular metabolism of apo B-100 lipoproteins along the VLDL----LDL cascade.