EVIDENCE FOR ROLES OF RADICALS IN PROTEIN OXIDATION IN ADVANCED HUMANATHEROSCLEROTIC PLAQUE

Oxidative damage might be important in atherogenesis. Oxidized lipids are present at significant concentrations in advanced human plaque, al though tissue antioxidants are mostly present at normal concentrations . Indirect evidence of protein modification (notably derivatization of lysine) or oxidation has been obtained by immunochemical methods; the specificities of these antibodies are unclear. Here we present chemic al determinations of six protein-bound oxidation products: dopa, o-tyr osine, m-tyrosine, dityrosine, hydroxyleucine and hydroxyvaline, some of which reflect particularly oxy-radical-mediated reaction pathways, which seem to involve mainly the participation of transition-metal ion s. We compared the relative abundance of these oxidation products in n ormal intima, and in human carotid plaque samples with that observed a fter radiolytically generated hydroxyl radical attack on BSA in vitro. The close similarities in relative abundances in the latter two circu mstances indicate that hydroxyl radical damage might occur in plaque. The relatively higher level of dityrosine in plaque than that observed after radiolysis suggests the additional involvement of HOCl-mediated reactions in advanced plaque.