Effect of genetic disruption of poly (ADP-ribose) synthetase on delayed production of inflammatory mediators and delayed necrosis during myocardial ischemia-reperfusion injury

Zequan Yang, Basilia Zingarelli, Csaba Szabo

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77 Scopus citations

Abstract

The nuclear enzyme poly (ADP ribose) synthetase (PARS) has been shown to play an important role in the pathogenesis of various forms of ischemia or reperfusion injury and circulatory shock. Recent studies demonstrated that inhibition or genetic inactivation of PARS is beneficial in the early phase of myocardial reperfusion injury. The aim of the present study was to investigate whether inactivation of PARS influences the delayed myocardial necrosis and the production of the proinflammatory cytokine tumor necrosis factorα (TNFα), the anti-inflammatory cytokine interleukin-10 (IL-10), and the free radical nitric oxide in the late stage of myocardial reperfusion injury. The results demonstrate that genetic disruption of PARS provides marked protection against the delayed myocardial ischemia and reperfusion injury. In addition, in the absence of functional PARS, a suppression of TNFa, IL-10, and nitric oxide production was found. These findings provide direct evidence that PARS activation participates in the development of delayed cell injury and delayed mediator production in myocardial reperfusion injury.

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Keywords

  • Cytokines
  • Heart
  • Ischemia
  • Nitric oxide
  • Peroxynitrite
  • Reperfusion

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

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