The interaction between human plasma lipoproteins and connective tissue glycosaminoglycans.

The interaction between human plasma lipoproteins and glycosaminoglycans has been studied by use of gels consisting of cross-linked hyaluronic acid and of sulfated glycosaminoglycans covalently attached to agarose (Sepharose 4B). When chromatographed on a column of granulated hyaluronic acid gel at physiological pH and ionic strength, very low density (VLDL), low density (LDL), and high density (HDL) lipoproteins were shown to emerge with the void volume, indicating that no significant binding to the polysaccharide had occurred. Equilibration of the same lipoproteins with glycosaminoglycan-substituted agarose gels at pH 7.4 showed that VLDL as well as LDL were bound to gels containing heparin, dermatan sulfate, heparan sulfate, and chondroitin 4-sulfate, provided the ionic strength was sufficiently low. In contrast, HDL and acetylated specimens of VLDL and LDL did not bind to the gels at any ionic strength. The observed interactions have been interpreted as an ionic binding of positively charged amino groups on apolipoprotein B to negatively charged groups on the glycosaminoglycans. The range of ionic strength at which each lipoprotein was released from a polysaccharide was relatively narrow and depended on the type of polysaccharide. For the release of half the amounts of VLDL, or LDL, bound to gels of heparin, dermatan sulfate, heparan sulfate, and chondroitin C-sulfate, ionic strengths of 0.26,0.15,0.09, and 0.08, respectively, were required. The results were interpreted in terms of an electrostatic binding between polyvalent anionic and cationic sites with the charge density of the polysaccharide being an important parameter for the strength of the ionic bond. At equal charge density, polysaccharides containing L-iduronic acid seemed to interact more strongly than those containing D-glucuronic acid.