1. A proliferative burst during preadolescence establishes the final cardiomyocyte number.
- Author
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Naqvi N, Li M, Calvert JW, Tejada T, Lambert JP, Wu J, Kesteven SH, Holman SR, Matsuda T, Lovelock JD, Howard WW, Iismaa SE, Chan AY, Crawford BH, Wagner MB, Martin DI, Lefer DJ, Graham RM, and Husain A
- Subjects
- Animals, Cell Separation, Male, Mice, Mice, Inbred C57BL, Myocytes, Cardiac physiology, Triiodothyronine metabolism, Cell Differentiation, Cell Proliferation, Heart growth & development, Myocytes, Cardiac cytology
- 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., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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