As AMP-activated protein kinase (AMPK) controls protein translation, an anti-hypertrophic effect of AMPK has been suggested. However, there is no genetic evidence to confirm this hypothesis. We investigated the contribution of AMPK alpha 2 in the control of cardiac hypertrophy by using AMPK alpha 2-/- mice submitted to isoproterenol. The isoproterenol-induced cardiac hypertrophy, measured by left ventricular mass and histological examination, was significantly higher in AMPK alpha 2-/- than in WT animals. Moreover, the intensification of cardiac hypertrophy found in AMPK alpha 2-/- mice can be linked to the abnormal basal overstimulation of the p70 ribosomal S6 protein kinase, an enzyme known to regulate protein translation and cell growth. In conclusion, this work shows that AMPK alpha 2 plays a role of brake for the development of cardiac hypertrophy. (C) 2008 Elsevier Inc. All rights reserved.