Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation

David C. Zebrowski, Charlotte H. Jensen, Robert Becker, Fulvia Ferrazzi, Christina Baun, Svend Hvidsten, Søren P. Sheikh, Brian D. Polizzotti, Ditte C. Andersen, Felix B. Engel*

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Abstrakt

After birth cardiomyocytes undergo terminal differentiation, characterized by binucleation and centrosome disassembly, rendering the heart unable to regenerate. Yet, it has been suggested that newborn mammals regenerate their hearts after apical resection by cardiomyocyte proliferation. Thus, we tested the hypothesis that apical resection either inhibits, delays, or reverses cardiomyocyte centrosome disassembly and binucleation. Our data show that apical resection rather transiently accelerates centrosome disassembly as well as the rate of binucleation. Consistent with the nearly 2-fold increased rate of binucleation there was a nearly 2-fold increase in the number of cardiomyocytes in mitosis indicating that the majority of injury-induced cardiomyocyte cell cycle activity results in binucleation, not proliferation. Concurrently, cardiomyocytes undergoing cytokinesis from embryonic hearts exhibited midbody formation consistent with successful abscission, whereas those from 3 day-old cardiomyocytes after apical resection exhibited midbody formation consistent with abscission failure. Lastly, injured hearts failed to fully regenerate as evidenced by persistent scarring and reduced wall motion. Collectively, these data suggest that should a regenerative program exist in the newborn mammalian heart, it is quickly curtailed by developmental mechanisms that render cardiomyocytes post-mitotic.

OriginalsprogEngelsk
Artikelnummer8362
TidsskriftScientific Reports
Vol/bind7
Antal sider11
ISSN2045-2322
DOI
StatusUdgivet - 21. aug. 2017

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