Mechanisms of Metal Ion-Dependent Oxidation of Human Low Density Lipoprotein

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Abstract
Although either copper or iron is essential for oxidation of human low density lipoprotein (LDL) by vascular cells, the mechanism is unknown. In our experiments copper- and iron-mediated LDL oxidation was found to proceed by different mechanisms. Oxidation of LDL by iron requires superoxide and proceeds by a hydroxyl radical-independent mechanism involving reduction of iron from the ferric to the ferrous form. In contrast, copper-mediated LDL oxidation involves direct reduction of copper from the cupric to the cuprous form by LDL.