title: Angiotensin-generated reactive oxygen species in brain and pathogenesis of cardiovascular diseases.
abstract: CONCLUSIONS
  Overproduction of angiotensin II (Ang II) in brain contributes to the pathogenesis of cardiovascular diseases. One of the most promising theses that emerged during the last decade is that production of reactive oxygen species (ROS) and activation of redox-dependent signaling cascades underlie those Ang II actions. This review summarizes our status of understanding on the roles of ROS and redox-sensitive signaling in brain Ang II-dependent cardiovascular diseases, using hypertension and heart failure as illustrative examples.
  
  
  BACKGROUND
  ROS generated by NADPH oxidase, mitochondrial electron transport chain, and proinflammatory cytokines activates mitogen-activated protein kinases and transcription factors, which in turn modulate ion channel functions and ultimately increase neuronal activity and sympathetic outflow in brain Ang II-dependent cardiovascular diseases. Antioxidants targeting ROS have been demonstrated to be beneficial to Ang II-induced hypertension and heart failure via protection from oxidative stress in brain regions that subserve cardiovascular regulation.
  
  
  RESULTS
  Intra-neuronal signaling and the downstream redox-sensitive proteins involved in controlling the neuronal discharge rate, the sympathetic outflow, and the pathogenesis of cardiovascular diseases need to be identified. The cross talk between Ang II-induced oxidative stress and neuroinflammation in neural mechanisms of cardiovascular diseases also warrants further elucidation.
  
  
  CONCLUSIONS
  Future studies are needed to identify new redox-based therapeutics that work not only in animal models, but also in patients suffering from the prevalent diseases. Upregulation of endogenous antioxidants in the regulation of ROS homeostasis is a potential therapeutic target, as are small molecule- or nanoformulated conjugate-based antioxidant therapy.
authors.affiliation: Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital , Kaohsiung, Taiwan, Republic of China .
authors.forename: Samuel H H
authors.initials: SH
authors.lastname: Chan
authors.forename: Julie Y H
authors.initials: JY
authors.lastname: Chan
mesh_terms: D000804:Angiotensin II / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D000804:Angiotensin II