Interaction of hyaluronic acid-linked phosphatidylethanolamine (HyPE) with LDL and its effect on the susceptibility of LDL lipids to oxidation

The amphiphilic polysaccharide hyaluronic acid-linked phosphatidylethanolamine (HyPE), synthesized by covalently binding dipalmitoyl-phosphatidylethanolamine (DPPE) to short chain hyaluronic acid (mol. wt. ≃ 30 000), interacts with low-density lipoproteins (LDL), to form a 'sugar-decoration' of the LDL surface. This results in an increase in the apparent size of the LDL particles, as studied by photon correlation spectroscopy, and in broadening of the ¹H NMR signals of the LDL's phospholipids. Experiments conducted with fluorescently-labeled HyPE indicate that the interaction of HyPE with LDL involves incorporation of the hydrocarbon chains of this amphiphilic polysaccharide into the outer monolayer of the LDL. This interaction also inhibits the copper-induced oxidation of the LDL polyunsaturated fatty acids, avoiding oxidation altogether when the concentration of HyPE is higher than a tenth of the concentration of the LDL's phospholipids. This can not be attributed to competitive binding of copper by HyPE. We propose that the protection of LDL lipids against copper-induced oxidation is due to formation of a sugar network around the LDL.