A static pressure sensitive receptor APJ promote H9c2 cardiomyocyte hypertrophy via PI3K-autophagy pathway

This study is designed to investigate whether APJ receptor acts as a sensor in static pressure-induced cardiomyocyte hypertrophy and to investigate the mechanism of PI3K-autophagy pathway. The left ventricular hypertrophy rat model was established by coarctation of abdominal aorta. H9c2 rat cardiomyocytes were cultured in the presence of static pressure which was given by a custom-made pressure incubator. The results revealed that the expression of apelin/APJ system, PI3K, Akt and their phosphorylation were significantly increased in the operation group. Static pressure up-regulated the APJ expression, PI3K phosphorylation, Akt phosphorylation, LC3-II/I and beclin-1 expression in cardiomyocytes. APJ shRNA pGPU6/Neo-rat-399, PI3K inhibitor LY294002, Akt inhibitor 1701-1 blocked the up-regulation of APJ, PI3K phosphorylation, Akt phosphorylation, LC3-II/I and beclin-1 expression, respectively. Moreover, static pressure increased the diameter, volume, protein content of cells, and these could be reversed when the cells were treated with pGPU6/Neo-rat-399, LY294002, and autophagy inhibitor 3-methyladenine, respectively. These results suggested that static pressure up-regulates APJ expression to promote cardiomyocyte hypertrophy by a PI3K-autophagy pathway.