The hippo pathway in heart development, regeneration, and diseases

Q Zhou, L Li, B Zhao, KL Guan - Circulation research, 2015 - Am Heart Assoc
Q Zhou, L Li, B Zhao, KL Guan
Circulation research, 2015Am Heart Assoc
The heart is the first organ formed during mammalian development. A properly sized and
functional heart is vital throughout the entire lifespan. Loss of cardiomyocytes because of
injury or diseases leads to heart failure, which is a major cause of human morbidity and
mortality. Unfortunately, regenerative potential of the adult heart is limited. The Hippo
pathway is a recently identified signaling cascade that plays an evolutionarily conserved
role in organ size control by inhibiting cell proliferation, promoting apoptosis, regulating fates …
The heart is the first organ formed during mammalian development. A properly sized and functional heart is vital throughout the entire lifespan. Loss of cardiomyocytes because of injury or diseases leads to heart failure, which is a major cause of human morbidity and mortality. Unfortunately, regenerative potential of the adult heart is limited. The Hippo pathway is a recently identified signaling cascade that plays an evolutionarily conserved role in organ size control by inhibiting cell proliferation, promoting apoptosis, regulating fates of stem/progenitor cells, and in some circumstances, limiting cell size. Interestingly, research indicates a key role of this pathway in regulation of cardiomyocyte proliferation and heart size. Inactivation of the Hippo pathway or activation of its downstream effector, the Yes-associated protein transcription coactivator, improves cardiac regeneration. Several known upstream signals of the Hippo pathway such as mechanical stress, G-protein–coupled receptor signaling, and oxidative stress are known to play critical roles in cardiac physiology. In addition, Yes-associated protein has been shown to regulate cardiomyocyte fate through multiple transcriptional mechanisms. In this review, we summarize and discuss current findings on the roles and mechanisms of the Hippo pathway in heart development, injury, and regeneration.
Am Heart Assoc