Pathways for oxidation of low density lipoprotein by myeloperoxidase: tyrosyl radical, reactive aldehydes, hypochlorous acid and molecular chlorine.
Many lines of evidence implicate oxidation of low density lipoprotein (LDL) in the pathogenesis of atherosclerosis, a chronic inflammatory disease. The physiologically relevant mechanisms have not been identified, but phagocytic white cells may play an important role because macrophage-rich lesions characterize the disorder. Recent studies have shown that myeloperoxidase, a heme enzyme secreted only by phagocytes, is present in human atherosclerotic tissue. The enzyme is a potent catalyst of LDL oxidation in vitro, it co-localizes with macrophages in lesions, and it generates products that are detectable in atherosclerotic plaque. These findings suggest that myeloperoxidase may promote LDL oxidation in the artery wall. This article reviews the enzyme's ability to generate a range of oxidants, including tyrosyl radical, reactive aldehydes, hypochlorous acid and molecular chlorine. These products have the potential to damage host molecules as well as microbes, suggesting a mechanism that may contribute to atherosclerotic vascular disease.
Heinecke
J W
JW
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. heinecke@im.wustl.edu
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000503:physiopathology; D002713:Chlorine / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D000447:Aldehydes; D008078:Cholesterol, LDL; D005609:Free Radicals; D008077:Lipoproteins, LDL; D016877:Oxidants; C099252:oxidized low density lipoprotein; C066447:tyrosyl radical Y(D); D014443:Tyrosine; D002713:Chlorine; D006997:Hypochlorous Acid; D009195:Peroxidase