Peroxynitrite and nitrosative stress in heart failure: Role of matrix metalloproteinases (MMPs) and poly(ADP)-ribose polymerase (PARP)

Heart failure is the major cause of hospitalization, morbidity and mortality worldwide. There is considerable evidence suggesting that the increased production of reactive oxygen and nitrogen species play a crucial role in the pathogenesis of various forms of myocardial injury and heart failure. Peroxynitrite, a reactive nitrogen species produced from the diffusion-controlled reaction between nitric oxide and superoxide anion, has been shown to impair cardiac function via multiple mechanisms including activation of matrix metalloproteinases (MMPs) and nuclear enzyme poly(ADP-ribose) polymerase (PARP). Recent studies have demonstrated that pharmacological neutralization of peroxynitrite or inhibition of PARP provides significant benefits in various forms of heart failure. This chapter discusses the role of peroxynitrite and nitrosative stress and downstream pathways in various forms of heart failure.