Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, 02138, USA.
Massachusetts General Hospital, Cardiology Division and Corrigan Minehan Heart Center, Boston, MA, 02114, USA.
Nat Commun. 2018 Apr 25;9(1):1659. doi: 10.1038/s41467-018-04083-1.
Loss of cardiomyocytes is a major cause of heart failure, and while the adult heart has a limited capacity for cardiomyogenesis, little is known about what regulates this ability or whether it can be effectively harnessed. Here we show that 8 weeks of running exercise increase birth of new cardiomyocytes in adult mice (~4.6-fold). New cardiomyocytes are identified based on incorporation of N-thymidine by multi-isotope imaging mass spectrometry (MIMS) and on being mononucleate/diploid. Furthermore, we demonstrate that exercise after myocardial infarction induces a robust cardiomyogenic response in an extended border zone of the infarcted area. Inhibition of miR-222, a microRNA increased by exercise in both animal models and humans, completely blocks the cardiomyogenic exercise response. These findings demonstrate that cardiomyogenesis can be activated by exercise in the normal and injured adult mouse heart and suggest that stimulation of endogenous cardiomyocyte generation could contribute to the benefits of exercise.
心肌细胞的丧失是心力衰竭的一个主要原因，尽管成年心脏的心肌发生能力有限，但对于调节这种能力的因素知之甚少，也不知道是否可以有效地利用这种能力。在这里，我们发现 8 周的跑步运动可使成年小鼠产生新的心肌细胞（增加约 4.6 倍）。通过多同位素成像质谱（MIMS）检测 N-胸苷的掺入和单核/二倍体来识别新的心肌细胞。此外，我们证明心肌梗死后的运动可在梗死区域的扩展边界区引起强烈的心肌发生反应。在两种动物模型和人类中，运动增加的 microRNA miR-222 的抑制作用完全阻断了心肌发生的运动反应。这些发现表明，运动可以激活正常和受损的成年小鼠心脏中的心肌发生，并表明刺激内源性心肌细胞生成可能有助于运动的益处。
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