Chondroitin-4-sulfate protects high-density lipoprotein against copper-dependent oxidation

We investigated the effect of chondroitinsulphate (CS), the major glycosami noglycan of the arterial wall, on the oxidation of human high-density lipop rotein (HDL) by kinetic analysis, Chondroitin-4-sulfate (C4S) increased the lag time and reduced the maximum rate of HDL oxidation induced by Cu2+, as assessed by monitoring both conjugated diene formation and low-level chemi luminescence. On the contrary, chondroitin-6-sulfate (C6S) was ineffective, Dermatansulfate exhibited an inhibitory effect comparable to that of C4S. C4S protected also the protein moiety of HDL, as it reduced tryptophan dest ruction by lipid-oxidizing species and delayed the formation of fluorescent adducts between end products of lipid peroxidation and amino acid residues . Again, C6S was ineffective, C4S was able to bind Cu2+; this resulted in l ess Cu2+ available able for HDL oxidation and likely represented the mechan ism of the protective effect, Neither C4S nor C6S affected HDL oxidation by peroxyl radicals, indicating that free radical scavenging activity was not involved in the protective effect, These results suggest that C4S might pr event the oxidative modification of HDL in arterial wall, thus preserving i ts antiatherogenic potential for reverse cholesterol transport and, possibl y, for clearance of oxidized lipids. (C) 1999 Academic Press.