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Isolation, Culture and Transduction of Adult Mouse Cardiomyocytes
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Hippo signaling impedes adult heart regeneration

Todd Heallen1, Yuka Morikawa, John Leach

  • 1Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Development (Cambridge, England)
|November 21, 2013
PubMed

Insights

Hippo signaling normally prevents adult heart muscle cells from dividing. Inhibiting this pathway promotes cardiomyocyte regeneration and functional recovery after heart injury, offering a potential treatment for heart disease.

Area of Science:

  • Cardiovascular Biology
  • Regenerative Medicine
  • Cell Signaling

Background:

  • Heart failure, a leading cause of death, results from poor heart muscle regeneration after injury.
  • Endogenous mechanisms inhibiting mammalian cardiomyocyte regeneration remain largely unknown.
  • Hippo signaling, a known organ size regulator, has not been studied in adult cardiomyocyte renewal.

Purpose of the Study:

  • To investigate the role of Hippo signaling in adult cardiomyocyte renewal and regeneration.
  • To determine if modulating Hippo signaling can enhance heart repair after injury.

Main Methods:

  • Studied Hippo signaling in adult mouse cardiomyocytes.
  • Examined cardiomyocyte proliferation and regeneration after genetic Hippo deficiency.
  • Assessed functional recovery following myocardial infarction and cardiac apex resection in Hippo-deficient mice.

Main Results:

  • Unstressed, Hippo-deficient adult mouse cardiomyocytes re-enter the cell cycle and divide.
  • Hippo deficiency significantly enhances cardiomyocyte regeneration and functional recovery after myocardial infarction.
  • Hippo deficiency promotes cardiomyocyte proliferation in damaged adult hearts.

Conclusions:

  • Hippo signaling acts as an endogenous repressor of adult cardiomyocyte renewal and regeneration.
  • Targeting the Hippo pathway presents a promising therapeutic strategy for treating heart disease.
  • Modulating Hippo signaling could improve outcomes for patients with ischemic heart disease.

Keywords:
Cell cycleMouseProliferationRegeneration

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