EXTENSIVE NITRATION OF PROTEIN TYROSINES IN HUMAN ATHEROSCLEROSIS DETECTED BY IMMUNOHISTOCHEMISTRY

Oxidation of lipoproteins is important for the initiation and propagat ion of the atherosclerotic lesion and may involve secondary oxidants d erived from nitric oxide. Nitric oxide (NO) reacts at near diffusion l imited rates with superoxide (O-2.(-)) to form the strong oxidant, per oxynitrite (ONOO-). Nitration on the ortho position of tyrosine is a m ajor product of peroxynitrite attack on proteins. Nitrotyrosine was de tected in atherosclerotic lesions of formalin-fixed human coronary art eries with polyclonal and monoclonal antibodies. Binding was pronounce d in and around foamy macrophages within the atheroma deposits. Nitrat ion was also observed in early subintimal fatty streaks. Antibody bind ing was completely blocked by co-incubation with 10mM nitrotyrosine, b ut not by equivalent concentrations of aminotyrosine or phosphotyrosin e. The presence of nitrotyrosine indicates that oxidants derived from nitric oxide such as peroxynitrite are generated in human atherosclero sis and may be involved in its pathogenesis.