The regulation and function of the Hippo pathway in heart regeneration

Wiley Interdiscip Rev Dev Biol. 2019 Jan;8(1):e335. doi: 10.1002/wdev.335. Epub 2018 Aug 31.

Abstract

Heart failure caused by cardiomyocyte loss and fibrosis is a leading cause of death worldwide. Although current treatments for heart failure such as heart transplantation and left ventricular assist device implantation have obvious value, new approaches are needed. Endogenous adult cardiomyocyte renewal is measurable but inefficient and inadequate in response to extensive acute heart damage. Stimulating self-renewal of endogenous cardiomyocytes holds great promise for heart repair. Uncovering the genetic mechanisms underlying cardiomyocyte renewal is a critical step in developing new approaches to repairing the heart. Recent studies have revealed that the inhibition of the Hippo pathway is sufficient to promote the proliferation of endogenous cardiomyocytes, indicating that the manipulation of the Hippo pathway in the heart may be a promising treatment for heart failure in the future. We summarize recent findings that have shed light on the function of the Hippo pathway in heart regeneration. We also discuss the mechanisms by which Hippo pathway inhibition promotes heart regeneration and how the Hippo pathway responds to different types of injury or stress during the regenerative process. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration.

Keywords: Hippo pathway; ROS; heart failure; heart regeneration; mechanical stress.

Publication types

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

MeSH terms

  • Adult Stem Cells / transplantation*
  • Cell Proliferation / genetics
  • Cell Self Renewal / genetics
  • Heart / growth & development
  • Heart / physiopathology
  • Heart Failure / genetics
  • Heart Failure / physiopathology
  • Heart Failure / therapy*
  • Hippo Signaling Pathway
  • Humans
  • Myocytes, Cardiac / pathology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / genetics*
  • Regeneration / genetics*
  • Regeneration / physiology
  • Signal Transduction / genetics

Substances

  • Protein Serine-Threonine Kinases