Oxidative stress and heart failure.
Despite advances in treatment, chronic congestive heart failure carries a poor prognosis and remains a leading cause of cardiovascular death. Accumulating evidence suggests that reactive oxygen species (ROS) play an important role in the development and progression of heart failure, regardless of the etiology. Under pathophysiological conditions, ROS have the potential to cause cellular damage and dysfunction. Whether the effects are beneficial or harmful will depend upon site, source and amount of ROS produced, and the overall redox status of the cell. All cardiovascular cell types are capable of producing ROS, and the major enzymatic sources in heart failure are mitochondria, xanthine oxidases and the nonphagocytic NADPH oxidases (Noxs). As well as direct effects on cellular enzymatic and protein function, ROS have been implicated in the development of agonist-induced cardiac hypertrophy, cardiomyocyte apoptosis and remodelling of the failing myocardium. These alterations in phenotype are driven by redox-sensitive gene expression, and in this way ROS may act a potent intracellular second messengers. Recent experimental studies have suggested a possible causal role for increased ROS in the development of contractile dysfunction following myocardial infarction and pressure overload, however the precise contribution of different cellular and enzymatic sources involved remain under investigation.
Department of Cardiology, Guy's King's & St Thomas's School of Medicine, King's College London, London, U.K.
J A
JA
Byrne
D J
DJ
Grieve
A C
AC
Cave
A M
AM
Shah
D017209:Apoptosis; D006332:Cardiomegaly / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism
D017382:Reactive Oxygen Species; D014969:Xanthine Oxidase; D009247:NADH, NADPH Oxidoreductases