title: Hypoxia induces myocardial regeneration in zebrafish.
abstract: BACKGROUND
  Hypoxia plays an important role in many biological/pathological processes. In particular, hypoxia is associated with cardiac ischemia. which, although initially inducing a protective response, will ultimately lead to the death of cardiomyocytes and loss of tissue, severely affecting cardiac functionality. Although myocardial damage/loss remains an insurmountable problem for adult mammals, the same is not true for adult zebrafish, which are able to completely regenerate their heart after extensive injury. Myocardial regeneration in zebrafish involves the dedifferentiation and proliferation of cardiomyocytes to replace the damaged/missing tissue; at present, however, little is known about what factors regulate this process.
  
  
  RESULTS
  We surmised that ventricular amputation would lead to hypoxia induction in the myocardium of zebrafish and that this may play a role in regulating the regeneration of the missing cardiac tissue. Using a combination of O(2) perturbation, conditional transgenics, in vitro cell culture, and microarray analysis, we found that hypoxia induces cardiomyocytes to dedifferentiate and proliferate during heart regeneration in zebrafish and have identified a number of genes that could play a role in this process.
  
  
  CONCLUSIONS
  These results indicate that hypoxia plays a positive role during heart regeneration, which should be taken into account in future strategies aimed at inducing heart regeneration in humans.
authors.affiliation: The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Jopling
authors.forename: Guillermo
authors.initials: G
authors.lastname: Suñé
authors.forename: Adèle
authors.initials: A
authors.lastname: Faucherre
authors.forename: Carme
authors.initials: C
authors.lastname: Fabregat
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisua Belmonte
mesh_terms: D000818:Animals; D054337:Cell Dedifferentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006321:Heart / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D032383:Myocytes, Cardiac / Q000502:physiology; D012038:Regeneration; D015027:Zebrafish / Q000502:physiology*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit