Autophagic Regulation of Cardiomyocyte Survival and Heart Regeneration

Abstract

Autophagy is regarded as an essential cellular protective mechanism of cardiomyocytes against a panel of stresses such as myocardial infarction and isch- emia–reperfusion. Autophagy-dependent protection against such stresses is espe- cially important in cardiomyocytes, since adult cardiomyocytes are terminally differentiated cells and considered not to proliferate any more. However, this con- cept 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 cardiomyo- cytes can reenter the cell cycle and proliferate upon activation of YAP, a transcrip- tional 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 extracel- lular 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.