Abstract 17097: Acute Inflammation is Required for Regenerative Response in the Neonatal Mouse Heart
Introduction: The neonatal mouse heart retains regenerative ability up to 1 week after birth. The regenerative response is characterized by increased cardiomyocyte proliferation following apical resection. However, the mechanisms involved in the reactive cardiomyocyte proliferation are largely unknown. We hypothesized that the acute inflammation was required to activate the regenerative response.
Methods and Results: We induced sterile inflammation through apical intramyocardial microinjection of zymosan A. Similar to apical resection, zymosan A led to a significant increase of expression levels of inflammatory markers(il6,il1b and ccl3) and number of infiltrating Gr-1(1A8)+ neutrophils demonstrated by realtime PCR and immunofluorescence, whereas at the same time there were no apparent effects on cell viability and tissue integrity. To test whether the induced inflammation led to incresed cardiomyocyte proliferation, we performed the double immunostaining for Ki67 or pH3 and α-actinin. We found a significant increase of proliferating cardiomyocaytes in zymosan A injected hearts relative to PBS injected hearts 4 and 7 days after injection. We also detected a significantly increased Brdu+ cardiomyocytes in zymosan A injected hearts relative to PBS injected hearts 21 days after injection. To explore whether the inflammation was necessary for the regenerative response, we immunosuppressed the mice of resected hearts by administering the anti-inflammatory drug dexamethasone(Dex). Realtime PCR(il6,il1b and ccl3) and immunofluorescence (Gr-1(1A8)) confirmed the immunosuppression effect, while there were no effects on body weight, cardiomyocyte size and cell viability. We found apparently decreased number of Ki67 or pH3 positive cardiomyocyes in apical resected and Dex treated mice compared to resected and PBS treated mice. Moreover, the resected and Dex treated mice hearts displayed a significantly decreased Brdu+ cardiomyocytes 21 days after resection. Next, we found the apical resected and Dex treated mice cannot regenerate their hearts after 21 days, even 5 weeks after injury.
Conclusion: our results indicated the acute inflammation was required for regenerative response in 1-day-old mouse heart.
Author Disclosures: C. Han: None. Y. Nie: None. H. Lian: None. R. Liu: None. F. He: None. S. Hu: None.
- © 2014 by American Heart Association, Inc.