A proliferative burst during preadolescence establishes the final cardiomyocyte number

Nawazish Naqvi, Ming Li, John W. Calvert, Thor Tejada, Jonathan P. Lambert, Jianxin Wu, Scott H. Kesteven, Sara R. Holman, Torahiro Matsuda, Joshua D. Lovelock, Wesley W. Howard, Siiri E. Iismaa, Andrea Y. Chan, Brian H. Crawford, Mary B. Wagner, David I. K. Martin, David J. Lefer, Robert M. Graham, Ahsan Husain

Research output: Contribution to journalArticlepeer-review

170 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)795-807
Number of pages13
JournalCell
Volume157
Issue number4
DOIs
Publication statusPublished - 8 May 2014
Externally publishedYes

Keywords

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cell Separation
  • Heart/growth & development
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocytes, Cardiac/cytology
  • Triiodothyronine/metabolism

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