HUMAN ARTERIAL PROTEOGLYCANS INCREASE THE RATE OF PROTEOLYTIC FUSION OF LOW-DENSITY-LIPOPROTEIN PARTICLES

Low density lipoprotein (LDL) particles can undergo fusion in the arte rial intima, where they are bound to proteoglycans. Here we studied th e effect of human arterial proteoglycans on proteolytic fusion of LDL in vitro. For this purpose, an assay was devised based on fluorescence resonance energy transfer that allowed continuous monitoring of fusio n of proteoglycan-bound LDL particles, We found that addition of human arterial proteoglycans markedly increased the rate of proteolytic fus ion of LDL, The glycosaminoglycans isolated from the proteoglycans als o increased the rate of fusion, demonstrating that this effect was pro duced by the negatively charged sulfated polysaccharides In the proteo glycans, Furthermore, heparin, chondroitin 6-sulfate, and dextran sulf ate, three commercially available sulfated polysaccharides, also incre ased the rate of LDL fusion, with heparin and chondroitin g-sulfate be ing as effective as and dextran sulfate more effective than hu man pro teoglycans. The ability of the sulfated polysaccharides to increase th e rate of proteolytic fusion of LDL depended critically on their abili ty to form insoluble complexes with LDL, which, in turn, resulted in a n increased rate of LDL proteolysis and, in consequence, in an increas ed rate of LDL fusion, The results reveal a novel mechanism regulating LDL fusion and point to the potentially important role of arterial pr oteoglycans in the generation of LDL-derived lipid droplets in the art erial intima during atherogenesis.