Abstract 16546: microRNA(miR)-451 Regulates Cardiac Growth and Myocardial Reactive Oxidative Species (ROS) Level via Nrf2 and AMPK Pathways

The role of miR-451 in certain cardiac diseases was recently reported including ischemia/reperfusion and hypertrophic cardiomyopathy. Oxidative stress is known to involve in the above diseases. Currently the relationship between miR-451 and cardiac oxidative stress is unknown. We thus hypothesize that miR-451 act as a key mediator for cardiac hypertrophy via regulating myocardial ROS level and antioxidant pathways. We first compared the heart/body weight (HW/BW) ratio between age- & gender-matched miR-451 knockout (KO) and wild-type (WT) mice. Increase of HW/BW was found in KO mice (6.1±0.1 vs 4.8±0.1 mg/g in WT, p<0.01). Expression of fetal genes ANF (2.9-fold↑) and β-MHC (4.0-fold↑) was also significantly increased in KO hearts, as well as the ROS level (2.3-fold↑, p<0.05) in KO hearts. Consistently, both the protein expression and activation levels of the oxidation-regulating gene Nrf2 decreased the same extent (~33%↓, p<0.05) in KO hearts. In contrast, the protein expression of the direct antioxidants...