Regular articleActivation of the peroxynitrite-poly(adenosine diphosphate-ribose) polymerase pathway during neointima proliferation: A new target to prevent restenosis after endarterectomy
Clinical Relevance
Neointimal hyperplasia is a proliferative response to an arterial injury and a significant cause of bypass graft and angioplasty failure. Although there is growing evidence that reactive oxygen species and oxidative damage play an important role in restenosis, the molecular physiologic mechanism underlying the oxidative stress hypothesis is not fully understood. In the present study, we demonstrated that consistent with nitrosative stress, poly(adenosine diphosphate-ribose) polymerase (PARP) activation and apoptosis-inducing factor translocation were significantly increased in the neointima after endarterectomy. Neointima formation and inflammatory response after endarterectomy were attenuated by treatment with the PARP inhibitor INO-1001. PARP inhibition, therefore, may be a therapeutic strategy for prevention of restenosis after surgical vessel reconstruction.
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This work was supported by a grant from the German Research Foundation (SFB 414) to C. J. B. and G. S., and a grant from the Hungarian Research Fund (OTKA M041541) to C. S.
Competition of interest: none.