Binding of beta-VLDL to heparan sulfate proteoglycans requires lipoprotein lipase, whereas ApoE only modulates binding affinity.

The binding of beta-VLDL to heparan sulfate proteoglycans (HSPG) has been reported to be stimulated by both apoE and lipoprotein lipase (LPL). In the present study we investigated the effect of the isoform and the amount of apoE per particle, as well as the role of LPL on the binding of beta-VLDL to HSPG. Therefore, we isolated beta-VLDL from transgenic mice, expressing either APOE2(Arg158-->Cys) or APOE3-Leiden (E2-VLDL and E3Leiden-VLDL, respectively), as well as from apoE-deficient mice containing no apoE at all (Enull-VLDL). In the absence of LPL, the binding affinity and maximal binding capacity of all beta-VLDL samples for HSPG-coated microtiter plates was very low. Addition of LPL to this cell-free system resulted in a 12- to 55-fold increase in the binding affinity and a 7- to 15-fold increase in the maximal binding capacity (Bmax). In the presence of LPL, the association constant (Ka) tended to increase in the order Enull-VLDL<E2-VLDL<E3Leiden-VLDL, whereas Bmax increased in the reverse order: E3Leiden-VLDL approximately E2-VLDL<Enull-VLDL. Addition of LPL resulted in a marked stimulation of both Ka and Bmax for binding of beta-VLDL samples to J774 cells similar to that found for the binding to HSPG-LPL complexes. Our results indicate that both Ka and Bmax for binding of beta-VLDL to HSPG are increased more than 1 order of magnitude on addition of LPL. In addition, for the binding of beta-VLDL to HSPG-LPL complexes, the presence of apoE is not a prerequisite, but results in an increased binding affinity, depending on the apoE isoform used.