P21 activated kinase 1 (PAK1) protects heart from pressure overload induced pathological cardiac remodeling

P21 activated kinase 1 (PAK1) is a serine/threonine kinase that is activated in the heart by multiple stress signals. To explore the role of PAK1 in the heart, we performed transverse aortic constriction (TAC) surgery on transgenic (TG) mice that overexpress PAK1 and gene disrupted mice that lack PAK1 (KO) in the heart. Although PAK1 overexpression resulted in moderate cardiac hypertrophy, TAC‐induced cardiac growth was dramatically reduced in PAK1 TG mice as compared to wild type (WT) littermates. This was accompanied by improved cardiac function and decreased myocyte apoptosis, suggesting that PAK1 signaling can protect against pressure overload‐induced pathological cardiac remodeling. Conversely, PAK1 KO mice displayed mild cardiac chamber dilation and compromised heart function at baseline. Not surprisingly, TAC induced greater structural and functional damage in PAK1 KO heart than in WT heart. These results demonstrate that PAK1 is required not only for baseline cardiac homeostasis, but also for cardiac adaptation to pathological stress. In summary, PAK1 conveys a vital protective signal that might be beneficial during pathological cardiac hypertrophy and heart failure.