Lipoprotein-proteoglycan interactions at a silica surface membrane

摘要

Proteoheparan sulfate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic polysugar side chains are stretched ont into the blood substitute solution representing a receptor site for specific lipoprotion binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques showing that low density lipoprotein (LDL) strongly deposited at the proteoheparan suflate, particularly in the presence of Ca~(2+). On the other hand, high density lipoportein (HDL) bound to heparan sulfate proteoglycan (HS-PG) protected against LDL docking even at high LDL and Ca~(2+) concentrations and completely suppressed calcification of the proteoglycan-lipo-protein complex. These findings correlate well with those obtained from clinical investigations on risk factors for arteriosclerosis. The most important patient-oriented finding was the at least four times higher affinity constant of HDL binding to the proteoglycan receptor as compared to LDL docking. Therefore, under normal in vivo conditions most of the proteoglycan receptors are occupied by HDL and in this way shielded against LDL binding. Since compettion is the domainant rule at the receptor site, the ternary complex HS-PG/LDL/Ca~(2+) aggregation can be reversed by HDL. Altogether, the proteoglycan coated hydrophobic silica surface used in these experiments, mimics the endothelial cell membrane in quite a perfect manner with respect to lipoprotein interactions at the blood-endothelium-matrix interface.