The role of miR-34a in AngⅡinduced myocardial hypertrophy via alteration of AMPK/mTOR signal pathway

HUANG Jionghua; LIN Yuhui; DAI Wenjun; WU Jinlei; XIE Wenjie; CHEN Yongquan

doi:10.11958/20160435

Abstract：Objective To explore the effects of miR-34a and the alteration of AMPK/mTOR signal pathway on angiotensin (Ang)Ⅱ-stimulated cardiomyocytes hypertrophy. Methods Neonatal rat cardiomyocytes were cultrued in vitro and were divided into 3 groups:negative control for lentivirus carrying miR-34a group (NC), AngⅡplus lentivirus carrying negative control group (AngⅡ+NC) and AngⅡplus lentivirus carrying miR-34a group (AngⅡ+miR-34a). The relative cell area was detected by confocal microscopy. The expression of miR-34a and hypertrophy-related genes (ANP and β-MHC) were analyzed by real time PCR. The AMPK/mTOR signal pathway was measured by Western blot assay. Results Compared to NC group, the relative cell area was increased in AngⅡ+NC group (P<0.05). But compared with AngⅡ+NC group, the relative cell area was decreased in AngII+miR-34a group (P<0.05). Moreover, compared with NC group, the expression of miR-34a was decreased, and the expression of hyperthophy-related genes(ANP and β-MHC) was up-regulated in AngⅡ+NC group. However, the expression of miR-34a was decreased, and the expression of hyperthophy-related genes (ANP and β-MHC) was down-regulated (P<0.05). Finally, compared to NC group, the ratio of phosphop-AMPK/AMPK was significantly induced in AngII + NC group, but the ratio of phosphop-mTOR/mTOR was significantly decreased (P<0.05). However, compared to AngⅡ+NC group, the ratio of phosphop-AMPK/AMPK was significantly decreased in AngII + miR-34a group, but the ratio of phosphop-mTOR/mTOR was significantly increased (P<0.05). Conclusion miR-34a is able to inhibit myocardial hypertrophy of neonatal rat cardiomyocytes, and its mechanism is partly carried out by the alteration of the signal pathway of AMPK/mTOR.