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Autophagic Regulation of Cardiomyocyte Survival and Heart Regeneration

  • Toshihiko Aki
  • Kanako Noritake
  • Kana Unuma
  • Koichi Uemura
Chapter
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

Autophagy is regarded as an essential cellular protective mechanism of cardiomyocytes against a panel of stresses such as myocardial infarction and ischemia–reperfusion. Autophagy-dependent protection against such stresses is especially important in cardiomyocytes, since adult cardiomyocytes are terminally differentiated cells and considered not to proliferate any more. However, this concept of adult cardiomyocyte nonproliferation has recently been challenged by many studies. Although the presence of cardiac stem cells in adult heart remains a subject of debate, there is ample evidence for the presence of cardiac progenitor cells that can differentiate into several heart-resident cells. Furthermore, adult cardiomyocytes can reenter the cell cycle and proliferate upon activation of YAP, a transcriptional coactivator downstream of the hippo pathway. In addition, cardiac cells in the epicardium can also transform into cardiofibroblasts, which contribute to tissue regeneration by filling damaged parts of tissue with themselves as well as extracellular matrix. This process seems to be executed through epithelial–mesenchymal transition (EMT). Autophagy has been supposed to participate in the maintenance of cardiomyocyte homeostasis not only by protecting the cells against stress, but also by facilitating regeneration. In this chapter, we discuss the possible roles of autophagy in protection as well as the promotion of regeneration of cardiomyocytes by regulating the hippo/YAP pathway and EMT.

Keywords

Autophagy Cardiomyocyte proliferation Hippo pathway YAP Epithelial to mesenchymal transition 

Abbreviations

8-OHdG

8-Oxo-2′-deoxyguanosine

Atg

Autophagy-related

BH

Bcl-2 homologous

CMA

Chaperone-mediated autophagy

CTGF

Connective tissue growth factor

EMT

Epithelial–mesenchymal transition

FIP200

Focal adhesion kinase family interacting protein of 200 kDa

LAMP

Lysosome-associated membrane protein

LATS

Large tumor suppressor homolog

LC3

Microtubles-associated protein light chain3

MET

Mesenchymal–epithelial transition

Mst

Mammalian STE20-like protein kinase

RASSF1

Ras association domain-containing protein 1

ROS

Reactive oxygen species

Sav

Salvador homolog

TAZ

Transcriptional coactivator with PDZ-binding motif

TEAD

Transcriptiona enhancer-associated domain

ULK

Unc-51-like kinase

YAP

Yes-associated protein

Notes

Acknowledgments

This work was supported in part by MEXT KAKENHI Grant Number JP25460862. The authors declare no conflicts of interest.

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© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Toshihiko Aki
    • 1
  • Kanako Noritake
    • 1
  • Kana Unuma
    • 1
  • Koichi Uemura
    • 1
  1. 1.Department of Forensic MedicineTokyo Medical and Dental UniversityTokyoJapan

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