Kinetics of lipid peroxidation in mixtures of HDL and LDL, mutual effects

In view of the proposed central role of LDL oxidation in atherogenesis and the established role of HDL in reducing the risk of atherosclerosis, severa l studies were undertaken to investigate the possible effect of HDL on LDL peroxidation. Since these investigations yielded contradictory results, we have conducted systematic kinetic studies on the oxidation in mixtures of H DL and LDL induced by different concentrations of copper, 2, 2'-azo bis (2- amidinopropane) hydrochloride (AAPH) and myeloperoxidase (MPO). These studi es revealed that oxidation of LDL induced either by AAPH or MPO is inhibite d by HDL under all the studied conditions, whereas copper-induced oxidation of LDL is inhibited by HDL at low copper/lipoprotein ratio but accelerated by HDL at high copper/lipoprotein ratio. The antioxidative effects of HDL are only partially due to HDL-associated enzymes, as indicated by the findi ng that reconstituted HDL, containing no such enzymes, inhibits peroxidatio n induced by low copper concentration. Reduction of the binding of copper t o LDL by competitive binding to the HDL also contributes to the antioxidati ve effect of HDL. The acceleration of copper-induced oxidation of LDL by HD L may be attributed to the hydroperoxides formed in the "more oxidizable" H DL, which migrate to the "less oxidizable" LDL and enhance the oxidation of the LDL lipids induced by bound copper. This hypothesis is supported by th e results of experiments in which native LDL was added to oxidizing lipopro tein at different time points. When the native LDL was added prior to decom position of the hydroperoxides in the oxidizing lipoprotein, the lag preced ing oxidation of the LDL was much shorter than the lag observed when the na tive LDL was added at latter stages, after the level of hydroperoxides beca me reduced due to their copper-catalyzed decomposition. The observed depend ence of the interrelationship between the oxidation of HDL and LDL on the o xidative stress should be considered in future investigations regarding the oxidation of lipoprotein mixtures. (C) 2001 Elsevier Science Inc.