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Volume 272, Number 40, Issue of October 3, 1997 pp. 25283-25288
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Human Arterial Proteoglycans Increase the Rate of Proteolytic Fusion of Low Density Lipoprotein Particles

(Received for publication, March 11, 1997, and in revised form, May 27, 1997)

Markku O. Pentikäinen , Erno M. P. Lehtonen , Katariina Öörni , Sari Lusa ^§ , Pentti Somerharju ^§ , Matti Jauhiainen ^¶ and Petri T. Kovanen

From the  Wihuri Research Institute, 00140 Helsinki, the ^§ Department of Medical Chemistry, Institute of Biomedicine, 00014 University of Helsinki, and the ^¶ Department of Biochemistry, National Public Health Institute, 00300 Helsinki, Finland

Low density lipoprotein (LDL) particles can undergo fusion in the arterial intima, where they are bound to proteoglycans. Here we studied the 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 fusion of proteoglycan-bound LDL particles. We found that addition of human arterial proteoglycans markedly increased the rate of proteolytic fusion of LDL. The glycosaminoglycans isolated from the proteoglycans also increased the rate of fusion, demonstrating that this effect was produced by the negatively charged sulfated polysaccharides in the proteoglycans. Furthermore, heparin, chondroitin 6-sulfate, and dextran sulfate, three commercially available sulfated polysaccharides, also increased the rate of LDL fusion, with heparin and chondroitin 6-sulfate being as effective as and dextran sulfate more effective than human proteoglycans. The ability of the sulfated polysaccharides to increase the rate of proteolytic fusion of LDL depended critically on their ability to form insoluble complexes with LDL, which, in turn, resulted in an increased rate of LDL proteolysis and, in consequence, in an increased rate of LDL fusion. The results reveal a novel mechanism regulating LDL fusion and point to the potentially important role of arterial proteoglycans in the generation of LDL-derived lipid droplets in the arterial intima during atherogenesis.

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