Altered susceptibility to in vitro oxidation of LDL in LDL complexes and LDL aggregates

Low density lipoprotein (LDL) is known to form complexes with polysulfated compounds, like heparin, dextran sulfate (DS), and chondroitin sulfate. In particular, chondroitin 6-sulfate (C6S)-rich proteoglycans of the arterial intima can associate with LDL, resulting in accumulation of LDL in atherosclerotic lesions. Besides LDL complex formation, LDL self-aggregation has been recently suggested to play a role in atherogenesis. Oxidative modification of LDL has also been implicated as a factor in the generation of the atherosclerotic plaque. Assuming that LDL self-aggregation may alter the molecule's susceptibility to oxidative modification, we have studied the sensitivity of LDL in LDL a aggregates as well as in insoluble and soluble LDL-C6S, LDL-heparin, and LDL-DS complexes to in vitro oxidation by cooper ions. Complexing the LDL with C6S and heparin resulted in an increased susceptibility of LDL to in vitro oxidation, whereas the oxidation of LDL complexed with DS was unaffected. In great contrast to the oxidation of LDL in LDL complexes, the in vitro oxidation of LDL in LDL aggregates (self-aggregation by denaturation) was strongly reduced. The results suggest that complex or aggregate formation may alter the susceptibility of the lipoprotein to oxidative modification and finally its metabolic fate or biological activity.