Regulation of Myocardial Cell Growth and Death by the Hippo Pathway.

Stress in the heart causes loss of cardiomyocytes (CMs), the accumulation of which leads to heart failure, a major cause of clinical mortality. The improvement of CM survival and facilitation of CM regeneration are major goals in treatment for heart failure. The Hippo pathway is an evolutionarily conserved signaling mechanism that regulates organ size by controlling both apoptosis and cell proliferation. The main components of the Hippo pathway, including Mst1/2, Lats1/2 and Yes-associated protein (Yap), are present in the mammalian heart and play an important role in regulating the growth and death of CMs. Recent research in the cardiac field has demonstrated that Yap, a key downstream transcriptional cofactor in the Hippo signaling pathway, plays a crucial role in regulating survival and proliferation/hypertrophy of CMs. Increasing lines of evidence suggest that Yap promotes regeneration of the heart after myocardial infarction. In this review, we summarize the current knowledge regarding the roles and functions of the Hippo pathway in the heart, with a particular emphasis on the role of Yap in regulating growth and death of CMs. (Circ J 2016; 80: 1511-1519).