A growing role for the Hippo signaling pathway in the heart

Heart disease is a major cause of clinical morbidity and mortality, and a significant health and economic burden worldwide. The loss of functional cardiomyocytes, often a result of myocardial infarction, leads to impaired cardiac output and ultimately heart failure. Therefore, efforts to improve cardiomyocyte viability and stimulate cardiomyocyte proliferation remain attractive therapeutic goals. Originally identified in Drosophila, the Hippo signaling pathway is highly conserved from flies to humans and regulates organ size through modulation of both cell survival and proliferation. This is particularly relevant to the heart, an organ with limited regenerative ability. Recent work has demonstrated a critical role for this signaling cascade in determining heart development, homeostasis, injury and the potential for regeneration. Here we review the function of canonical and non-canonical Hippo signaling in cardiomyocytes, with a particular focus on proliferation and survival, and how this impacts the stressed adult heart.