Prostaglandin E2 promotes post-infarction cardiomyocyte replenishment by endogenous stem cells

Authors

  • Ying-Chang Hsueh,

    1. Institute of Basic Medical Sciences, National Cheng Kung University and Hospital, Tainan, Taiwan
    2. Institute of Clinical Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan
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    • These authors contributed equally to this paper.
  • Jasmine M F Wu,

    1. Institute of Basic Medical Sciences, National Cheng Kung University and Hospital, Tainan, Taiwan
    2. Institute of Clinical Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan
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    • These authors contributed equally to this paper.
  • Chun-Keung Yu,

    1. Institute of Basic Medical Sciences, National Cheng Kung University and Hospital, Tainan, Taiwan
    2. Department of Microbiology and Immunology, National Cheng Kung University and Hospital, Tainan, Taiwan
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  • Kenneth K Wu,

    1. Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan
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  • Patrick C H Hsieh

    Corresponding author
    1. Institute of Basic Medical Sciences, National Cheng Kung University and Hospital, Tainan, Taiwan
    2. Institute of Clinical Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan
    3. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
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Abstract

Although self-renewal ability of adult mammalian heart has been reported, few pharmacological treatments are known to promote cardiomyocyte regeneration after injury. In this study, we demonstrate that the critical period of stem/progenitor cell-mediated cardiomyocyte replenishment is initiated within 7 days and saturates on day 10 post-infarction. Moreover, blocking the inflammatory reaction with COX-2 inhibitors may also reduce the capability of endogenous stem/progenitor cells to repopulate lost cells. Injection of the COX-2 product PGE2 enhances cardiomyocyte replenishment in young mice and recovers cell renewal through attenuating TGF-β1 signaling in aged mice. Further analyses suggest that cardiac stem cells are PGE2-responsive and that PGE2 may regulate stem cell activity directly through the EP2 receptor or indirectly by modulating its micro-environment in vivo. Our findings provide evidence that PGE2 holds great potential for cardiac regeneration.

Synopsis

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Although lost cardiomyocytes could be replenished after injury, the efficiency is extremely low. Here, the authors show that PGE2 treatment at a critical time period improves stem cell-mediated cardiac repair in young mice and restores it in aged animals.

  • Stem cell-derived cardiomyocyte replenishment occurs within 7 days of injury.
  • An early inflammatory signal regulates cardiac regeneration after infarction.
  • PGE2 stimulates cardiomyocyte replenishment mediated by cardiac stem cells.
  • PGE2 rescues the cardiomyocyte replenishment capacity that is lost in aged mice.