Oxidation of low density lipoprotein by iron or copper at acidic pH

Oxidized low density lipoprotein (LDL) may play a significant role in atherosclerosis. We have investigated the effect of pH on the oxidation of LDL by iron or copper. When LDL was oxidized by iron in the presence of cysteine in either Hanks' balanced salt solution (HBSS) or Ham's F-10 medium, an acidic pH greatly decreased the lag period and increased the rate of formation of hydroperoxides and thiobarbituric acid-reactive substances (TEARS), and increased its uptake by macrophages. There was a dose-dependent increase of LDL oxidation at acidic pH in the presence of increasing concentrations of cysteine. When LDL was oxidized by copper in HBSS, an acidic pH increased the lag phase before the rapid formation of conjugated dienes, hydroperoxides, and TEARS, but increased its uptake by macrophages. Similar results were obtained using Ham's F-10 medium. Cysteine (100 mu m) inhibited the modification of LDL by copper in HBSS at both pH 7.4 and 5.5. As atherosclerotic lesions may be acidic, these observations may help to explain why LDL oxidation occurs locally at these sites.