Myeloperoxidase-generated oxidants and atherosclerosis.
Atherosclerosis is a chronic inflammatory process where oxidative damage within the artery wall is implicated in the pathogenesis of the disease. Mononuclear phagocytes, an inflammatory cell capable of generating a variety of oxidizing species, are early components of arterial lesions. Their normal functions include host defense and surveillance through regulated generation of diffusible radical species, reactive oxygen or nitrogen species, and HOCl (hypochlorous acid). However, under certain circumstances an excess of these oxidizing species can overwhelm local antioxidant defenses and lead to oxidant stress and oxidative tissue injury, processes implicated in the pathogenesis of atherosclerosis. This review focuses on oxidation reactions catalyzed by myeloperoxidase (MPO), an abundant heme protein secreted from activated phagocytes which is present in human atherosclerotic lesions. Over the past several years, significant evidence has accrued demonstrating that MPO is one pathway for protein and lipoprotein oxidation during the evolution of cardiovascular disease. Multiple distinct products of MPO are enriched in human atherosclerotic lesions and LDL recovered from human atheroma. However, the biological consequences of these MPO-catalyzed reactions in vivo are still unclear. Here we discuss evidence for the occurrence of MPO-catalyzed oxidation reactions in vivo and the potential role MPO plays in both normal host defenses and inflammatory diseases like atherosclerosis.
Podrez
E A
EA
Department of Cell Biology,Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Abu-Soud
H M
HM
Hazen
S L
SL
D000447:Aldehydes / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D002384:Catalysis; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D009574:Nitro Compounds / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D000447:Aldehydes; D000596:Amino Acids; D005609:Free Radicals; D008077:Lipoproteins, LDL; D009574:Nitro Compounds; D016877:Oxidants; D014443:Tyrosine; D009195:Peroxidase; C087259:3-chlorotyrosine