Cu2+-induced low density lipoprotein peroxidation is dependent on the initial O-2 concentration: An O-2 consumption study

Atherosclerotic plaques form in the arterial intima, where low density lipo protein (LDL) is thought to be oxidatively modified at sites which may cont ain catalytic amounts of copper in the presence ai low O-2 tension. We have investigated O-2 consumption during LDL peroxidation induced by Cu ions in viiro and found two phases: a lag phase followed by a phase of rapid O-2 c onsumption. The length of the lag phase was dependent on Ci(2+) and on init ial O-2 concentrations; increasing either decreased the lag time; however, LDL concentration had no effect. LDL-induced Cu2+ reduction, however, was n ot affected by low initial O-2 concentrations, suggesting that O-2 is not r equired for LDL-mediated reduction of Cu2+. Following the lag phase, O-2 co nsumption was dependent upon LDL or initial O-2 concentrations; Cu2+ concen trations had little effect, suggesting that the propagation phase is more d ependent on the presence of LDL lipids and O-2 as substrates for the reacti on. In summary, LDL peroxidation takes place in the presence of Cu2+ at low O-2 tension; however, the reaction is dependent upon initial O-2 concentra tions; increases shorten the lag phase and accelerate O-2 consumption.