title: Nrf2 protects against maladaptive cardiac responses to hemodynamic stress.
abstract: BACKGROUND
  Reactive oxygen species (ROS) play an important role in the maintenance of cardiovascular homeostasis. The present study sought to determine whether nuclear factor erythroid-2 related factor 2 (Nrf2), a master gene of the endogenous antioxidant defense system, is a critical regulator of the cardiac hypertrophic response to pathological stress.
  
  
  RESULTS
  Cardiac hypertrophy and dysfunction were established in mice by transverse aortic constriction (TAC). Nrf2 expression was transiently increased and then declined to the basal level while impairment of cardiac function proceeded. The knockout of Nrf2 (Nrf2(-/-)) did not cause any apparent structural and functional abnormalities in the unstressed heart. However, Nrf2(-/-) mice after TAC developed pathological cardiac hypertrophy, significant myocardial fibrosis and apoptosis, overt heart failure, and increased mortality, which were associated with elevated myocardial levels of 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine and a complete blockade of the myocardial expression of several antioxidant genes. Overexpression of Nrf2 dramatically inhibited hypertrophic factor-induced ROS production and growth in both cardiomyocytes and cardiac fibroblasts, whereas knockdown of Nrf2 exerted opposite effects in both cells.
  
  
  CONCLUSIONS
  These findings demonstrate that activation of Nrf2 provides a novel mechanism to protect the murine heart against pathological cardiac hypertrophy and heart failure via suppressing oxidative stress.
authors: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors: Jinqing
authors: J
authors: Li
authors: Tomonaga
authors: T
authors: Ichikawa
authors: Luis
authors: L
authors: Villacorta
authors: Joseph S
authors: JS
authors: Janicki
authors: Gregory L
authors: GL
authors: Brower
authors: Masayuki
authors: M
authors: Yamamoto
authors: Taixing
authors: T
authors: Cui
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006439:Hemodynamics; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000166:cytology / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D011336:Probability; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D015854:Up-Regulation; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species