Abstract 249: Neonatal Mouse Hearts Do Not Regenerate after Severe Cryoinjury
Introduction: In contrast to adult zebrafish, mammalian adult hearts cannot regenerate in response to tissue damage. Interestingly, neonatal mouse hearts have regenerative capacity similar to adult zebrafish after ventricular resection. Zebrafish hearts regenerate in a similar manner after cryoinjury compared to other injury types (ventricular resection and genetic ablation); however scar tissue forms and it takes much more time to resolve the scar and regenerate after cryoinjury. It remains to be determined if neonatal mouse hearts regenerate after cryoinjury, which is thought to be the injury model most similar to damage caused by infarction than resection.
Hypothesis: Neonatal mouse hearts respond to different types of injuries differently; there might be a limit to the regenerative capacity of neonatal mouse hearts.
Methods: To determine if neonatal mouse hearts respond to different types of injuries differently, we established a cryoinjury model by utilizing a cryoprobe pre-chilled in liquid nitrogen placed at the anteriolateral ventricular wall. At different time points, cardiac functions were determined and the hearts were collected for histological analysis.
Results: In contrast to ventricular resection, neonatal mouse hearts fail to regenerate at 21, 60 and 120 days after severe (transmural) cryoinjury. Minimum scar tissues remain after mild (non-transmural) cryoinjury. Echocardiography showed severe impairment of cardiac functions after severe cryoinjury. Epicardial activation and new coronary vessel formation occured after cryoinjury. However, we did not observe increased cardiomyocyte proliferation after severe cryoinjury; this is consistent with the finding that neonatal mouse hearts regenerate after ventricular resection by cardiomyocyte proliferation. When neovascularization is blocked by induction of a VEGF-sequestering soluble receptor (sVEGFR1), neonatal mouse hearts cannot survive after severe cryoinjury and form a more extensive scar following a mild cryoinjury.
Conclusion: Neonatal mouse hearts do not regenerate after severe transmural injury due to failure to undergo cardiomyocyte proliferation. Furthermore, neovascularization is essential for the survival and heart regeneration of neonatal mice.
- © 2013 by American Heart Association, Inc.