Cardiomyocyte proliferation contributes to heart growth in young humans
Cardiomyocyte proliferation contributes to heart growth in young humans
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DOI：
10.1073/pnas.1214608110
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发表时间：
2013-01-22
影响因子：
11.1
通讯作者：
Kuehn, Bernhard
中科院分区：
文献类型：
--
作者：
Mollova, Mariya;Bersell, Kevin;Kuehn, Bernhard
人的心脏在出生后的发育过程中被认为是通过心肌细胞(心肌细胞)的增大而不是增殖来生长的。然而，最近的研究表明，心肌细胞增殖是动物心脏生长和再生的一种机制。结合成年人心肌细胞周转的证据，这表明心肌细胞增殖可能在出生到青春期之间的心脏发育期间发挥着未被认识的作用。我们在一组年龄为0-59岁(n=36)的健康心脏上检测了左心室的细胞生长机制，从而验证了这一假说。心肌细胞有丝分裂和胞质分裂的比例在婴儿中最高，到20岁时下降到较低水平。虽然心肌细胞有丝分裂在整个生命过程中都可以检测到，但20岁后心肌细胞胞质分裂不明显。在第一年到20岁之间，左室心肌细胞的数量增加了3.4倍，这与我们根据测量的心肌细胞周期活动所做的预测是一致的。我们的发现表明，心肌细胞的增殖有助于年轻人心脏的发育。这表明，儿童和青少年可能能够再生心肌，心肌细胞异常增殖可能参与了影响这一人群的心肌疾病，这些疾病可能是可以通过刺激心肌细胞增殖来治疗的。
The human heart is believed to grow by enlargement but not proliferation of cardiomyocytes (heart muscle cells) during postnatal development. However, recent studies have shown that cardiomyocyte proliferation is a mechanism of cardiac growth and regeneration in animals. Combined with evidence for cardiomyocyte turnover in adult humans, this suggests that cardiomyocyte proliferation may play an unrecognized role during the period of developmental heart growth between birth and adolescence. We tested this hypothesis by examining the cellular growth mechanisms of the left ventricle on a set of healthy hearts from humans aged 0-59 y (n = 36). The percentages of cardiomyocytes in mitosis and cytokinesis were highest in infants, decreasing to low levels by 20 y. Although cardiomyocyte mitosis was detectable throughout life, cardiomyocyte cytokinesis was not evident after 20 y. Between the first year and 20 y of life, the number of cardiomyocytes in the left ventricle increased 3.4-fold, which was consistent with our predictions based on measured cardiomyocyte cell cycle activity. Our findings show that cardiomyocyte proliferation contributes to developmental heart growth in young humans. This suggests that children and adolescents may be able to regenerate myocardium, that abnormal cardiomyocyte proliferation may be involved in myocardial diseases that affect this population, and that these diseases might be treatable through stimulation of cardiomyocyte proliferation.