Novel roles of PAK1 in the heart.

Our work and others' over the past few years have led to the identification of new roles of PAK1 in cardiac physiology, such as the regulation of cardiac ion channel and actomyosin function. More recent studies have revealed that PAK1-deficient mice were vulnerable to cardiac hypertrophy and readily progress to failure under sustained pressure overload and susceptible to ischemia/reperfusion injury. Our further study indicated that the PAK1 activator FTY720 was able to prevent this pressure overload-induced hypertrophy in wild-type mice without compromising their cardiac functions. A cardiac protective effect against ischemia/reperfusion injury by FTY720 was also observed in both rat and mouse models by us and others. Thus, these studies suggest that PAK1 is more important in the heart than previously thought, in particular a therapeutic potential of PAK1 activators. In the future, in-depth investigations are required to further substantiate our hypotheses on mechanisms for PAK1 function in the heart and to explore a therapeutic potential of FTY720 and other PAK1 activators in heart disease conditions.