“AKT”ing Lessons for Stem Cells: Regulation of Cardiac Myocyte and Progenitor Cell Proliferation

Cardiac development and postnatal growth depend on activation of AKT, but initial strategies to improve myocardial repair using AKT were stymied by undesirable corollary alterations in myocardial structure and function. These unfortunate precedents were based on high-level expression of constitutively activated AKT, predominantly in the cytoplasm of the cell. Based on subsequent studies establishing that activated AKT accumulates in the nucleus, we reasoned that the location of AKT, not simply the activity level, would be a critical determinant of the phenotypic outcome resulting from AKT activation. Using myocardial-specific expression of nuclear-targeted AKT (AKT/nuc), the proliferation of myocardial stem and progenitor cell populations is enhanced, casting new light on the implementation of AKT activity as a molecular interventional approach for treatment of cardiomyopathic damage resulting from acute injury, chronic stress, or the debilitating changes of aging.