A comparative study of low-density lipoprotein interaction with glycosaminoglycans

Abstract

The association between low-density lipoprotein (LDL) and a series of well characterized dermatan and chondroitin sulfates has been investigated by means of the fluorescence anisotropy technique with competition experiments using a fluorescein-labeled high LDL-affinity heparin fraction as a reference. Preparations of glycosaminoglycan (GAG) with sulfation degrees varying over a wide range, as obtained by fractionation or by chemical modification, were chosen for this study. The influence of chain length, which had been found sizeable in a former study of heparin affinity for LDL, was taken into account with an empirical correction of dissociation constants. After this correction, a linear relationship was found between the logarithm of dissociation constants and the number of sulfate groups per disaccharide unit, n s, both for dermatan and chondroitin sulfates, and for heparins. At comparable n s values, however, dermatan sulfates and heparins, which contain L-iduronic acid in their backbone, show higher LDL-affinity than chondroitin sulfates, which contain only D-glucuronic acid. Though confirming a non-specific, predominantly electrostatic interaction between GAGs and LDL, these results indicate modulation of LDL affinity by the polysaccharide backbone.