Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia.
Cell. 2014 May 8;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 ~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.
人们普遍认为围产期心肌细胞的终末分化会阻止胞质分裂，从而导致双核化，并限制损伤后的再生修复。这表明，在青春期前，心脏的生长应该完全通过心肌细胞的肥大来实现，此时在小鼠中，心脏质量在数周内增加数倍。在这里，我们表明，甲状腺激素激增会在出生后第 15 天激活 IGF-1/IGF-1-R/Akt 通路，并启动短暂但强烈的增殖爆发，主要是双核心肌细胞。这种增殖使心肌细胞数量增加约 40%，导致心脏和心肌细胞生长之间出现巨大差异。此外，出生后第 15 天对心脏损伤的反应介于出生后第 2 天和第 21 天之间，这进一步表明心肌细胞的增殖能力在围产期后仍持续存在。如果在人类中得到复制，这可能为心脏病的新型再生治疗方法提供可能。
