Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family
Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family
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DOI：
10.1073/pnas.1208863110
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发表时间：
2013-01-02
影响因子：
11.1
通讯作者：
Sadek, Hesham A.
中科院分区：
文献类型：
--
作者：
Porrello, Enzo R.;Mahmoud, Ahmed I.;Sadek, Hesham A.
我们最近确定了一个短暂的时期，在出生后的发展，当哺乳动物的心脏保留显着的再生潜力后，切断心室尖。然而，一个主要的未解决的问题是，新生小鼠的心脏是否也可以再生，以应对心肌缺血，最常见的人类心力衰竭的先兆。在这里，我们诱导1日龄小鼠缺血性心肌梗死（MI），发现这导致广泛的心肌坏死和收缩功能障碍。值得注意的是，新生儿心脏通过预先存在的心肌细胞的增殖，产生了强大的再生反应，导致在21天内完全恢复功能。此外，我们发现miR-15家族的microRNA通过抑制出生后心肌细胞增殖来调节新生儿心脏再生。最后，我们证明了从出生后早期到成年期抑制miR-15家族可以增加成人心脏中的肌细胞增殖，并改善成人MI后的左心室收缩功能。我们的结论是，新生哺乳动物的心脏可以再生心肌梗死后，通过增殖预先存在的心肌细胞和miR-15家族有助于出生后心脏再生能力的丧失。
We recently identified a brief time period during postnatal development when the mammalian heart retains significant regenerative potential after amputation of the ventricular apex. However, one major unresolved question is whether the neonatal mouse heart can also regenerate in response to myocardial ischemia, the most common antecedent of heart failure in humans. Here, we induced ischemic myocardial infarction (MI) in 1-d-oldmice and found that this results in extensive myocardial necrosis and systolic dysfunction. Remarkably, the neonatal heart mounted a robust regenerative response, through proliferation of preexisting cardiomyocytes, resulting in full functional recovery within 21 d. Moreover, we show that the miR-15 family of microRNAs modulates neonatal heart regeneration through inhibition of postnatal cardiomyocyte proliferation. Finally, we demonstrate that inhibition of the miR-15 family from an early postnatal age until adulthood increases myocyte proliferation in the adult heart and improves left ventricular systolic function after adult MI. We conclude that the neonatal mammalian heart can regenerate after myocardial infarction through proliferation of preexisting cardiomyocytes and that the miR-15 family contributes to postnatal loss of cardiac regenerative capacity.