The cell-autonomous and non-cell-autonomous roles of the Hippo pathway in heart regeneration

J Mol Cell Cardiol. 2022 Jul;168:98-106. doi: 10.1016/j.yjmcc.2022.04.018. Epub 2022 May 5.


Cardiomyocytes are differentiated heart muscle cells with minimal self-renewal ability. Thus, loss of cardiomyocytes from cardiovascular disease and injury cannot be effectively replenished. Recent studies in animal models have indicated that induction of endogenous cardiomyocyte proliferation is essential for cardiac renewal and that inhibiting the Hippo signaling pathway can stimulate cardiomyocyte proliferation and heart regeneration. Increasing evidence has suggested that cardiomyocyte proliferation requires a permissive microenvironment that consists of multiple cell types. In this review, we summarize recent studies that highlight how the Hippo pathway regulates heart regeneration through cell-autonomous and non-cell-autonomous mechanisms. We also discuss recent translational studies in large animal models that demonstrate the therapeutic potential of targeting the Hippo pathway in the treatment of heart disease.

Keywords: Cardiac regeneration; Cell communication; Heart failure; Hippo pathway; Large animal model; Proliferation.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Heart / physiology
  • Hippo Signaling Pathway*
  • Myocytes, Cardiac / metabolism
  • Protein Serine-Threonine Kinases*
  • Signal Transduction / physiology


  • Protein Serine-Threonine Kinases