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Sci Rep. 2017 Aug 21;7(1):8362. doi: 10.1038/s41598-017-08947-2.

Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation.

Author information

1
Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 12, 91054, Erlangen, Germany.
2
Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology (Odense University Hospital), Winsloewparken 213rd, 5000, Odense C, Denmark.
3
The Danish Regenerative Center (danishcrm.com); Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark.
4
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 10, 91054, Erlangen, Germany.
5
Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark.
6
Institute of Molecular Medicine/University of Southern Denmark, 5000, Odense C, Denmark.
7
Heart Center Translational Research Laboratory, Department of Cardiology, Boston Children's Hospital, Boston, MA, 02115, USA.
8
Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA.
9
Clinical Institute/University of Southern Denmark, 5000, Odense C, Denmark.
10
Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 12, 91054, Erlangen, Germany. Felix.Engel@uk-erlangen.de.
11
Muscle Research Center Erlangen (MURCE), Erlangen, Germany. Felix.Engel@uk-erlangen.de.

Abstract

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.

PMID:
28827644
PMCID:
PMC5567176
DOI:
10.1038/s41598-017-08947-2
[Indexed for MEDLINE]
Free PMC Article

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