Increased circulating levels of 3-nitrotyrosine autoantibodies: marker for or maker of cardiovascular disease?

3-nitrotyrosine formation is an oxidative protein modification that was first discovered in vivo in the early 1990s by Beckman and colleagues.1,2 The biological relevance of this process was extensively investigated in the subsequent years and further facilitated by the development of 3-nitrotyrosine– specific antibodies.3 Protein tyrosine nitration is mainly mediated by 3 biochemical processes (Figure): (1) by peroxynitrite (ONOO ) formation,4–6 the reaction product of nitric oxide (NO) and superoxide (●O2 ); (2) by a (myelo)peroxidase-catalyzed nitrogen dioxide radical (●NO2) formation from hydrogen peroxide and nitrite;7,8 and (3) by a nonspecific formation of the nitrogen dioxide radical from nitric oxide in oxygenated buffers (reflecting rather artificial ex vivo conditions).