Role of oxidative-nitrosative stress and downstream pathways in various forms of cardiomyopathy and heart failure.
Heart failure is the major cause of hospitalization, morbidity and mortality worldwide. Previous experimental and clinical studies have suggested that there is an increased production of reactive oxygen species (ROS: superoxide, hydrogen peroxide, hydroxyl radical) both in animals and in patients with acute and chronic heart failure. The possible source of increased ROS in the failing myocardium include xanthine and NAD(P)H oxidoreductases, cyclooxygenase, the mitochondrial electron transport chain and activated neutrophils among many others. The excessively produced nitric oxide (NO) derived from NO synthases (NOS) has also been implicated in the pathogenesis of chronic heart failure (CHF). The combination of NO and superoxide yields peroxynitrite, a reactive oxidant, which has been shown to impair cardiac function via multiple mechanisms. Increased oxidative and nitrosative stress also activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP), which importantly contributes to the pathogenesis of cardiac and endothelial dysfunction associated with myocardial infarction, chronic heart failure, diabetes, atherosclerosis, hypertension, aging and various forms of shock. Recent studies have demonstrated that pharmacological inhibition of xanthine oxidase derived superoxide formation, neutralization of peroxynitrite or inhibition of PARP provide significant benefit in various forms of cardiovascular injury. This review discusses the role of oxidative/nitrosative stress and downstream pathways in various forms of cardiomyopathy and heart failure.
Ungvári
Zoltan
Z
Department of Physiology, New York Medical College, Valhalla, 10595, USA.
Gupte
Sachin A
SA
Recchia
Fabio A
FA
Bátkai
Sándor
S
Pacher
Pál
P
D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000378:metabolism; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D014969:Xanthine Oxidase; D019255:NADPH Oxidases; D011065:Poly(ADP-ribose) Polymerases