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

The binding of beta-VLDL to heparan sulfate proteoglycans (HSPG) has been r eported 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 a poE 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 ei ther APOE*2(Arg158-->Cys) or APOE*3-Leiden (E2-VLDL and E3Leiden-VLDL, resp ectively), as well as from apoE-deficient mice containing no apoE at all (E null-VLDL). In the absence of LPL, the binding affinity and maximal binding capacity of all beta-VLDL samples for HSPG-coated microtiter plates was ve ry low. Addition of LPL to this cell-free system resulted in a 12- to 55-fo ld increase in the binding affinity and a 7- to 15-fold increase in the max imal binding capacity (B-max). In the presence of LPL, the association cons tant (K-a) tended to increase in the order Enull-VLDL<E2-VLDL<E3Leiden-VLDL , whereas B-max increased in the reverse order: E3Leiden-VLDL approximate t o E2-VLDL<Enull-VLDL. Addition of LPL resulted in a marked stimulation of b oth K-a and B-max for binding of beta-VLDL samples to J774 cells similar to that found for the binding to HSPG-LPL complexes. Our results indicate tha t both K-a and B-max for binding of beta-VLDL to HSPG are increased more th an 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 prerequisit e, but results in an increased binding affinity, depending on the apoE isof orm used.