Lipid peroxidation by myeloperoxidase
Degree GrantorUniversity of Canterbury
Degree NameMaster of Science
The oxidative modification of low density lipoprotein (LDL) is a requirement for the development of atherosclerosis. Heinecke's group has shown immunologically that myeloperoxidase (MPO) is present in human atherosclerotic lesions, both extracellularly and intracellularly (Daugherty et al., 1994). The enzyme MPO has a potent oxidising potential and is responsible for a large number of the reactants produced during the immune response (Weiss, 1989). Therefore, the neutrophil enzyme MPO has recently been implicated in in vivo LDL oxidation. A few studies exist which suggest that MPO is capable of peroxidising lipids and free fatty acids directly via its peroxidase cycle (Hazell et al., 1994; Stelmaszynska et al., 1992). However, these studies only contain a small reference to this activity. Thus, it is not yet conclusively established whether MPO alone is capable of initiating lipid peroxidation, the primary objective of this study. The present study has demonstrated that myeloperoxidase and its model peroxidase, horseradish peroxidase, are capable of initiating lipid peroxidation of linoleic acid micelles. This raises the possibility that MPO has a physiological role in the oxidation of LDL and consequently atherosclerosis. It also has implications for other inflammatory diseases where it is a possibility that MPO induced lipid peroxidation may mediate tissue injury.