Hypoxia Induces Myocardial Regeneration in Zebrafish
- Jopling, C., Suñè, G., Faucherre, A., Fabregat, C., and Izpisúa Belmonte, J.C.
- Circulation 126(25): 3017-3027 (Journal)
- Registered Authors
- Faucherre, Adele, Izpisúa Belmonte, Juan Carlos, Jopling, Chris
- hypoxia, myocardial regeneration, zebrafish
- MeSH Terms
- Cell Dedifferentiation
- Cell Proliferation
- Cells, Cultured
- Hypoxia-Inducible Factor 1, alpha Subunit/physiology
- Myocytes, Cardiac/physiology
- 23151342 Full text @ Circulation
Background—Hypoxia plays an important role in many biological/pathological processes. In particular, hypoxia is associated with cardiac ischemia which, while initially inducing a protective response, will ultimately lead to the death of cardiomyocytes and loss of tissue, severely impacting cardiac functionality. While 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 following extensive injury. Myocardial regeneration in zebrafish involves the dedifferentiation and proliferation of cardiomyocytes to replace the damaged/missing tissue, however, at present 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 which 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.