A Proliferative Burst during Preadolescence Establishes the Final Cardiomyocyte Number
Open accessAbstract
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.
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Cardiac regeneration may occur following other types of damage, such as myocardial infarction or cryoinjury, which could leave a matrix beneficial for the repair process.
“we cannot exclude that cardiac regeneration may occur following other types of damage, such as myocardial infarction or cryoinjury (Haubner et al., 2012, Jesty et al., 2012, Naqvi et al., 2014, Strungs et al., 2013), that could leave a matrix beneficial for the repair process.”
From Response to Sadek et al. and Kotlikoff et al. (2014) · cites this paper as Naqvi et al., 2014
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Response to Sadek et al. and Kotlikoff et al.
Andersen, D. C., Jensen, C. H., & Sheikh, S. P. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.06.011 · Cited by 14 · see citing works
- Authors
- Naqvi, N., Li, M., Calvert, J. W., Tejada, T., Lambert, J. P., Wu, J., Kesteven, S. H., Holman, S. R., Matsuda, T., Lovelock, J. D., Howard, W. W., Iismaa, S. E., Chan, A. Y., Crawford, B. H., Wagner, M. B., Martin, D. I. K., Lefer, D. J., Graham, R. M., & Husain, A.
- Affiliations
- Emory University (US)
- Victor Chang Cardiac Research Institute (AU)
- Corresponding author
- Graham, Robert M.
- Husain, Ahsan
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 157
- Issue
- 4
- Pages
- 795-807
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4078902
- OpenAlex
- W2048506716
- Cited by
- 295
- References
- 45
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 32 · 2023: 18 · 2022: 13 · 2021: 17 · 2020: 25 · 2019: 19 · 2018: 27 · 2017: 24 · 2016: 32 · 2015: 44 · 2014: 25
- FWCI
- 17.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000454)
- National Heart, Lung, and Blood Institute (R01HL098481, R01HL088488, HL079040, T32HL007745, P20HL113452, HL-088488, R01HL079040, HL098481)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- cardiomyocyte proliferation, cardiomyocyte number, late childhood, binucleation, cardiomyocyte hypertrophy, cardiac growth, cardiac regeneration, cardiac injury
- MeSH terms
- Animals, Cell Differentiation, Cell Separation, Heart, Male, Mice, Inbred C57BL, Triiodothyronine, Myocytes, Cardiac, Cell Proliferation, Mice
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