Reactive oxygen species, mitochondria, and NAD(P)H oxidases in the development and progression of heart failure.
Reactive oxygen species (ROS) released acutely in large amounts have been traditionally implicated in the cell death associated with myocardial infarction or reperfusion injury. These ROS can be released from the cardiac myocyte mitochondria, xanthine oxidase, and the phagocytic nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase. Interestingly, the chronic release of ROS has been recently linked to the development of left ventricular hypertrophy and heart failure progression. The chronic release of ROS appears to derive from the nonphagocytic NAD(P)H oxidase and mitochondria. Experimental data are accumulating suggesting that the release of ROS is required for the normal, physiologic activity of cardiac cells, but abnormal activation of the nonphagocytic NAD(P)H oxidase in response to neurohormones (angiotensin II, norepinephrine, tumor necrosis factor-a) has been shown to contribute to cardiac myocyte hypertrophy. Furthermore, the fibrosis, collagen deposition, and metalloproteinase activation involved in the remodeling of the failing myocardium are dependent on ROS released during the phenotypic transformation of fibroblasts to myofibroblasts associated with progression of end-stage heart failure. Future studies are necessary to identify the sources, mechanisms of activation of NAD(P)H oxidases, and downstream signaling targets implicated in the progression of chronic heart failure.
Sorescu
Dan
D
Emory University School of Medicine, Department of Medicine, Division of Cardiology, Atlanta, GA 30322, USA.
Griendling
Kathy K
KK
D000818:Animals; D017209:Apoptosis; D006332:Cardiomegaly / Q000209:etiology; D018450:Disease Progression; D004579:Electron Transport; D004789:Enzyme Activation; D006333:Heart Failure / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D017682:Myocardial Stunning / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D020257:Ventricular Remodeling
D017382:Reactive Oxygen Species; D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases