mAKAPβ signalosome: A potential target for cardiac hypertrophy

Pathological cardiac hypertrophy is the result of a prolonged increase in the workload of the heart that activates various signaling pathways such as MAPK pathway, PKA-dependent cAMP signaling, and CaN-NFAT signaling pathway which further activates genes for cardiac remodeling. Various signalosomes are present in the heart that regulates the signaling of physiological and pathological cardiac hypertrophy. mAKAPβ is one such scaffold protein that regulates signaling pathways involved in promoting cardiac hypertrophy. It is present in the outer nuclear envelope of the cardiomyocytes, which provides specificity of the target toward the heart. In addition, nuclear translocation of signaling components and transcription factors such as MEF2D, NFATc, and HIF-1α is facilitated due to the localization of mAKAPβ near the nuclear envelope. These factors are required for activation of genes promoting cardiac remodeling. Downregulation of mAKAPβ improves cardiac function and attenuates cardiac hypertrophy which in turn prevents the development of heart failure. Unlike earlier therapies for heart failure, knockout or silencing of mAKAPβ is not associated with side effects because of its high specificity in the striated myocytes. Downregulating expression of mAKAPβ is a favorable therapeutic approach toward attenuating cardiac hypertrophy and hence preventing heart failure. This review discusses mAKAPβ signalosome as a potential target for cardiac hypertrophy intervention.