A Proliferative Burst during Preadolescence Establishes the Final Cardiomyocyte Number

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

来源：Cell, 2014, 157(4): 795-807.

DOI：10.1016/j.cell.2014.03.035

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 similar to 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.

• 出版日期2014-5-8