Hypoxia induces myocardial regeneration in zebrafish

Chris Jopling, Guillermo Suñé, Adèle Faucherre, Carme Fabregat, Juan Carlos Izpisua Belmonte*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

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. METHODS AND 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 O2 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. CONCLUSION-: 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.

Original languageEnglish (US)
Pages (from-to)3017-3027
Number of pages11
JournalCirculation
Volume126
Issue number25
DOIs
StatePublished - Dec 18 2012
Externally publishedYes

Keywords

  • cardiac myocyte dedifferentiation
  • cardiac myocyte hypoxia
  • cardiac myocyte proliferation
  • regeneration zebrafish

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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