INTERACTION OF LDL AND LP[A] WITH HUMAN SKIN FIBROBLASTS

We have studied the interaction of LDL and Lp[a] with fibroblasts. Our studies suggest that Lp[a] does not effectively compete with LDL for binding to the LDL receptor, and does not efficiently suppress the activity of the intracellular enzyme HMG-CoA reductase. However, Lp[a(-)], formed by reduction of the disulfide bond between apo[a] and apoB, behaves much like homologous LDL, whether or not apo[a] is removed from the mixture, and in spite of the fact that one or more apoB disulfides may also have been cleaved. In our studies we also noted that Lp[a] often enhanced binding of I-125-LDL by fibroblasts. Further investigation has suggested that this interaction is time-dependent. Experiments in receptor-negative fibroblasts indicate that the enhancement is not related to the presence of the LDL receptor; however, it is inhibited by the removal of calcium from the medium. The presence of sialic acid at millimolar concentrations in the medium inhibits much of the Lp[a]-enhanced binding of I-125-LDL to the cells. These studies suggest that Lp[a] may in some way enhance LDL binding to cells, perhaps via interaction with cell surface glycosaminoglycans or proteoglycans or with collagen.