In response to mechanical load, cardiac hypertrophy (myocyte enlargement) is initially compensatory, but becomes a maladaptive process that leads to the development of heart failure. The high prevalence of pathological myocardial hypertrophy in cardiovascular disease coupled with a lack of effective treatment highlights a need for novel therapeutic strategies in this area.
Recently, a diverse family of scaffold proteins termed A-Kinase Anchoring Proteins have been identified and characterized, playing multiple important roles in the heart. In a recent study using a mouse model with a partial AKAPLbc (AKAP13) gene deletion, we demonstrate a crucial in vivo role for AKAP-Lbc-protein kinase D1 (PKD1) signaling in the development of compensatory hypertrophy in response to transverse aortic constriction (TAC)-induced pressure overload and neurohumoral stimulation by AT-II/PE treatment. Overall, our results show that AKAP-Lbc-PKD1 signaling is critical for transcriptional activation during the development of compensatory hypertrophy in vivo, under conditions of pathological hypertrophy. By defining and understanding regulation, downstream signaling and function of AKAP-Lbc- PKD1 signaling under pathological conditions, studies will determine whether AKAP-Lbc-PKD1 is a possible therapeutic target for treatment of cardiac dysfunction.