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Mechanisms of Metal Ion-Dependent Oxidation of Human Low Density Lipoprotein¹

Boston University School of Medicine, Whitaker Cardiovascular Institute, Boston, MA 02118

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.

KEY WORDS: • copper • iron • free radicals • atherosclerosis • human

¹ Presented as part of the symposium: "Formation, Metabolism and Physiologic Effects of Oxidatively Modified Low Density Lipoprotein" given at the Experimental Biology '95 meeting, Atlanta, GA, on April 12, 1995. This symposium was sponsored by the American Institute of Nutrition and was supported in part by Kraft General Foods, Inc. Guest editor for the symposium publication was Rachel Shireman, University of Florida, Gainesville, FL.

² To whom correspondence should be addressed: Biochemistry Department, Midwestern University, 555 31st Street, Downers Grove, IL 60515.