Does loss of AKAP121 precede induction of cardiac hypertrophy?

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Cheung, Anene
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The A‐kinase anchor proteins (AKAPs) are diverse regulators of cell function, acting as scaffolds to co‐localize the protein kinase A regulatory sub‐unit with target proteins, such as other kinases and phosphatases. We have previously demonstrated that over‐expression of AKAP121 in cardiomyocytes attenuates hypertrophy induced by isoproterenol. Furthermore, knockdown of AKAP121 expression induced spontaneous cardiomyocyte hypertrophy, suggesting that AKAP121 behaves as a potent anti‐hypertrophic regulator. In this study, mice underwent transverse aortic constriction (TAC), resulting in increased cardiac afterload and progressive hypertrophy. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting was used to examine expression of AKAP121 in banded and sham control animals. The degree of hypertrophy was assessed by heart weight to body weight or tibia length ratios. We hypothesized that AKAP121 expression will decrease soon after banding, prior to frank hypertrophy. Our current results demonstrate a correlation between loss of AKAP121 expression and induction of the hypertrophic gene program in response to pressure overload induced by thoracic aortic banding, thus indicating a potential role for AKAP121 as a regulator of the hypertrophic response in vivo. Our data also suggests that a sex‐specific mechanism may be involved in regulation of hypertrophic gene expression.