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Cell. 2014 May 8;157(4):795-807. doi: 10.1016/j.cell.2014.03.035.

A proliferative burst during preadolescence establishes the final cardiomyocyte number.

Author information

1
Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
2
Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia.
3
Division of Cardiothoracic Surgery, Department of Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, Atlanta, GA 30308, USA.
4
Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia; University of New South Wales, Kensington, NSW 2033, Australia.
5
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA; Center for Cardiovascular Biology, Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
6
Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
7
Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia; University of New South Wales, Kensington, NSW 2033, Australia. Electronic address: b.graham@victorchang.edu.au.
8
Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: ahusai2@emory.edu.

Abstract

It is widely believed that perinatal cardiomyocyte terminal differentiation blocks cytokinesis, thereby causing binucleation and limiting regenerative repair after injury. This suggests that heart growth should occur entirely by cardiomyocyte hypertrophy during preadolescence when, in mice, cardiac mass increases many-fold over a few weeks. Here, we show that a thyroid hormone surge activates the IGF-1/IGF-1-R/Akt pathway on postnatal day 15 and initiates a brief but intense proliferative burst of predominantly binuclear cardiomyocytes. This proliferation increases cardiomyocyte numbers by ~40%, causing a major disparity between heart and cardiomyocyte growth. Also, the response to cardiac injury at postnatal day 15 is intermediate between that observed at postnatal days 2 and 21, further suggesting persistence of cardiomyocyte proliferative capacity beyond the perinatal period. If replicated in humans, this may allow novel regenerative therapies for heart diseases.

PMID:
24813607
PMCID:
PMC4078902
DOI:
10.1016/j.cell.2014.03.035
[Indexed for MEDLINE]
Free PMC Article

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