Role of Nitrosative Stress and Poly(ADP-ribose) Polymerase Activation in Myocardial Reperfusion Injury

Gabor      Szabo; Susanne      Bahrle

Abstract

Ischemia and reperfusion injury leads to a complex pathophysiological process, which in turn results in the generation of free radicals. Peroxynitrite, a highly reactive species causes DNA single strand breaks, which activates the nuclear enzyme, poly (ADP-ribose) polymerase (PARP). The activation of PARP leads to an energy consuming inefficient repair cycle with subsequent depletion of NAD+ and ATP pools and necrotic cell death. The present review overviews the pathophysiological role of the peroxynitrite-PARP pathway in cardiac ischemia/reperfusion injury with special reference to the therapeutic potential of PARP inhibitors in the treatment of this disease.

Keywords: nitric oxide (no), peroxynitrite, ischemia reperfusion, dna damage, nad, parp inhibitor, reperfused myocardium, inflammatory pathways