Exercise induces new cardiomyocyte generation in the adult mammalian heart

Ana Vujic, Carolin Lerchenmüller, Ting-Di Wu, Christelle Guillermier, Charles P. Rabolli, Emilia Gonzalez, Samuel E. Senyo, Xiaojun Liu, Jean-Luc Guerquin-Kern, Matthew L. Steinhauser, Richard T. Lee () and Anthony Rosenzweig ()
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Ana Vujic: Harvard University
Carolin Lerchenmüller: Cardiology Division and Corrigan Minehan Heart Center
Ting-Di Wu: Institut Curie, PSL Research University
Christelle Guillermier: Harvard Medical School
Charles P. Rabolli: Cardiology Division and Corrigan Minehan Heart Center
Emilia Gonzalez: Harvard University
Samuel E. Senyo: Case Western Reserve University
Xiaojun Liu: Cardiology Division and Corrigan Minehan Heart Center
Jean-Luc Guerquin-Kern: Institut Curie, PSL Research University
Matthew L. Steinhauser: Harvard Medical School
Richard T. Lee: Harvard University
Anthony Rosenzweig: Cardiology Division and Corrigan Minehan Heart Center

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: Abstract 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 15N-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.

Date: 2018
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DOI: 10.1038/s41467-018-04083-1

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