AGT and cardiac hypertrophy: For example, SIRT1 exacerbated cardiac hypertrophy by promoting membrane localization and activation of Akt and phosphoinositide-dependent protein kinase 1, while impaired Akt activation in the hearts of SIRT1-deficient mice was related to decreased cardiac hypertrophy in response to physical exercise and Ang II.501 These opposite effects might be dependent on the degree of SIRT1 expression.502 For instance, the low (2.5-fold) or moderate (7.5-fold) overexpression of SIRT1 in the hearts of transgenic mice attenuated cardiac hypertrophy.