Editorial [Hot Topic: Role of Oxidative-Nitrostative Stress and Poly(ADP-ribose) Polymerase in Cardiovascular Pathophysiology (Guest Editor: Pal Pacher)]

Dysregulation of nitric oxide (NO) and increased oxidative stress have been implicated in the pathogenesis of cardiac and endothelial dysfunction associated with myocardial infarction, chronic heart failure, diabetes, atherosclerosis, hypertension, aging and various forms of shock. Peroxynitrite is a reactive oxidant produced from nitric oxide and superoxide, which impairs cardiovascular function via multiple mechanisms including activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP), also known as poly(ADP ribose) synthetase (PARS). When activated by DNA single-strand breaks, PARP initiates an energy-consuming cycle by transferring ADP ribose units from NAD+ to nuclear proteins. This process results in rapid depletion of the intracellular NAD+ and ATP pools, slowing the rate of glycolysis and mitochondrial respiration, eventually leading to cellular dysfunction and death. Moreover, PARP is involved in the expression of various inflammatory genes and mediators that contribute to cardiovascular pathophysiology. Overactivation of PARP represents an important mechanism of tissue damage in various pathological conditions associated with oxidative and nitrosative stress, including myocardial reperfusion injury, heart failure, stroke, shock and autoimmune β-cell destruction and diabetic complications. Recent studies have provided evidence that the neutralization of peroxynitrite or pharmacological inhibition of PARP is a promising new approach in the therapy of various forms of cardiovascular injury. This issue focuses on the role of oxidative-nitrosative stress and PARP activation in cardiovascular disorders and on novel emerging therapeutic strategies offered by neutralization of peroxynitrite and by inhibition of the PARP in these pathological conditions.