title: Angiotensin II-induced production of mitochondrial reactive oxygen species: potential mechanisms and relevance for cardiovascular disease.
abstract: CONCLUSIONS
  The role of reactive oxygen species (ROS) in angiotensin II (AngII) induced endothelial dysfunction, cardiovascular and renal remodeling, inflammation, and fibrosis has been well documented. The molecular mechanisms of AngII pathophysiological activity involve the stimulation of NADPH oxidases, which produce superoxide and hydrogen peroxide. AngII also increases the production of mitochondrial ROS, while the inhibition of AngII improves mitochondrial function; however, the specific molecular mechanisms of the stimulation of mitochondrial ROS is not clear.
  
  
  BACKGROUND
  Interestingly, the overexpression of mitochondrial thioredoxin 2 or mitochondrial superoxide dismutase attenuates AngII-induced hypertension, which demonstrates the importance of mitochondrial ROS in AngII-mediated cardiovascular diseases.
  
  
  RESULTS
  Although mitochondrial ROS plays an important role in normal physiological cell signaling, AngII, high glucose, high fat, or hypoxia may cause the overproduction of mitochondrial ROS, leading to the feed-forward redox stimulation of NADPH oxidases. This vicious cycle may contribute to the development of pathological conditions and facilitate organ damage in hypertension, atherosclerosis, and diabetes.
  
  
  CONCLUSIONS
  The development of antioxidant strategies specifically targeting mitochondria could be therapeutically beneficial in these disease conditions.
authors.affiliation: Free Radicals in Medicine Core, Division of Clinical Pharmacology, Vanderbilt University Medical Center , Nashville, Tennessee.
authors.forename: Sergey I
authors.initials: SI
authors.lastname: Dikalov
authors.forename: Rafal R
authors.initials: RR
authors.lastname: Nazarewicz
mesh_terms: D000804:Angiotensin II / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D000804:Angiotensin II; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D019255:NADPH Oxidases