Abstract
The phosphatidylinositol 3-kinase (PI3K) signaling pathway regulates multiple cellular processes including cell survival/apoptosis and growth. In the cardiac context, PI3Kalpha plays important roles in cardiac growth. We have shown that cardiac PI3K activity is highly regulated during development, with the highest levels found during the fetal-neonatal transition period and the lowest levels in the adult. There is a close relationship between cardiomyocyte proliferation and cardiac PI3K activity. In adult transgenic mice, however, the prolonged constitutive activation of PI3Kalpha in the heart results in hypertrophy. To develop a strategy to allow temporally controlled overexpression of cardiac PI3Kalpha, we engineered a tetracycline (tet) transactivator tet-off controlled transgenic mouse line with a conditional overexpression of a cardiac-specific fusion protein of the SH2 domain of p85 and p110alpha. Cardiac PI3K activity and Akt phosphorylation were significantly increased in adult mice after transgene induction following the removal of doxycycline for 2 wk. The heart weight-to-body weight ratio was not changed, and there were no signs of cardiomyopathy. The overexpression of PI3Kalpha resulted in increased left ventricular...Continue Reading
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