Targeting NF2-Hippo/Yap signaling pathway for cardioprotection after ischemia/reperfusion injury

Cardiac ischemia/reperfusion (I/R) injury is one of the most deleterious cardiovascular condition and a leading cause of mortality worldwide. The deprivation of oxygen and nutrient supply, due to blockage of coronary arteries, causes an oxidative stress on the myocardium leading to an irreversible loss of cardiomyocytes and impaired cardiac output. Timely reperfusion of coronary flow is necessary to reduce the oxidative stress and to limit myocardial injury. However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury. Recently, a series of studies have implicated Hippo signaling pathway in cardiomyocyte proliferation and survival during and after myocardial I/R injury (Figure 1) (1-4). However, the upstream modulators of Hippo-Yap pathway during myocardial I/R injury have not been identified.