Abstract 15637: AKT Regulates Cardiomyocyte Homeostasis by Regulating the Expression of the Voltage-Dependent L-Type Ca2+ Channel (Cav1.2)

Recent studies have shown that insulin-Akt-mTORC1 signaling contributes not only to embryonic and postnatal physiological heart growth, but also to adverse LV remodeling in pathological hypertrophy. However, the exact roles of Akt isoforms in maintaining cardiac function in the physiological setting remain to be elucidated. To determine the physiological role of the major cardiac Akt isoforms, Akt1 and Akt2, we used MerCreMer (MCM) / loxP DNA recombination to generate mice with inducible cardiomyocyte-restricted deletion of Akt1 and Akt2 (αMHC-MCM/Akt1flox/flox/Akt2flox/flox) (icAkt1/2-DKO). After administration of tamoxifen (TMX) (20mg/kg/day x 5days), Akt1 and Akt2 expression in the heart was nearly completely ablated 1 week after the last injection. Inducible deletion of Akt1 or Akt2 respectively had no impact on cardiac function. However, echocardiographic analysis revealed impaired fractional shortening developing at 2 weeks in icAkt1/2-DKO (23% decrease at 2 weeks and 48% decrease at 4 weeks) with a...