COPPER-INDUCED LDL PEROXIDATION INVESTIGATED BY H-1-NMR SPECTROSCOPY

Oxidatively modified LDL (oLDL) is thought to play a key role in the p athogenesis of atherosclerosis. We have studied Cu2+-induced peroxidat ion reactions of LDL and have elucidated the sequence of events which subsequently occur within LDL particles by H-1-NMR spectroscopy, Studi es of chloroform/methanol extracts show that LDL arachidonate is oxidi sed by Cu2+ at a higher rate and to a greater extent than linoleate, g iving isomeric hydroperoxides with predominantly trans,trans double-bo nds, whilst only cis,trans isomers were detected as intrinsic hydroper oxides in control LDL samples. These intrinsic hydroperoxides were not degraded during peroxidation, suggesting that they are not involved i n the initiation of Cu2+-induced peroxidation. Aldehydes arising from the decomposition of hydroperoxides were also detected, as well as sat urated fatty acids which were released into the external aqueous mediu m. Decomposition pathways of the two major isomeric hydroperoxides are discussed. Cu2+-induced oxidation of LDL cholesterol appears to occur only after hydroperoxide breakdown, with esterified cholesterol bring oxidised to a greater extent than free cholesterol. Phospholipid hydr olysis appeared to parallel the peroxidation of arachidonic acid, and the released lysophosphatidylcholine may become associated with apoB. These results suggest that hydroperoxide breakdown (probably in phosph olipids) may be a key event in the peroxidation process, leading to th e oxidation of cholesterol and propagation into the care of LDL.