Li Qiaoling, Xie Jun, Wang Bingjian, Li Ran, Bai Jian, Ding Liang, Gu Rong, Wang Lian, Xu Biao
Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China.
From the Department of Cardiology, Drum Tower Clinic Hospital, Nanjing Medical University, Nanjing, China.
PLoS One. 2016 Feb 25;11(2):e0148480. doi: 10.1371/journal.pone.0148480. eCollection 2016.
Pathological cardiomyocyte hypertrophy is associated with significantly increased risk of heart failure, one of the leading medical causes of mortality worldwide. MicroRNAs are known to be involved in pathological cardiac remodeling. However, whether miR-99a participates in the signaling cascade leading to cardiac hypertrophy is unknown. To evaluate the role of miR-99a in cardiac hypertrophy, we assessed the expression of miR-99a in hypertrophic cardiomyocytes induced by isoprenaline (ISO)/angiotensin-II (Ang II) and in mice model of cardiac hypertrophy induced by transverse aortic constriction (TAC). Expression of miR-99a was evaluated in these hypertrophic cells and hearts. We also found that miR-99a expression was highly correlated with cardiac function of mice with heart failure (8 weeks after TAC surgery). Overexpression of miR-99a attenuated cardiac hypertrophy in TAC mice and cellular hypertrophy in stimuli treated cardiomyocytes through down-regulation of expression of mammalian target of rapamycin (mTOR). These results indicate that miR-99a negatively regulates physiological hypertrophy through mTOR signaling pathway, which may provide a new therapeutic approach for pressure-overload heart failure.
病理性心肌细胞肥大与心力衰竭风险显著增加相关，心力衰竭是全球主要的医学致死原因之一。已知微小RNA参与病理性心脏重塑。然而，miR-99a是否参与导致心脏肥大的信号级联反应尚不清楚。为评估miR-99a在心脏肥大中的作用，我们检测了异丙肾上腺素（ISO）/血管紧张素-II（Ang II）诱导的肥大心肌细胞以及主动脉缩窄（TAC）诱导的心脏肥大小鼠模型中miR-99a的表达。在这些肥大细胞和心脏中评估了miR-99a的表达。我们还发现，miR-99a的表达与心力衰竭小鼠（TAC手术后8周）的心脏功能高度相关。miR-99a的过表达通过下调雷帕霉素靶蛋白（mTOR）的表达减轻了TAC小鼠的心脏肥大以及刺激处理的心肌细胞中的细胞肥大。这些结果表明，miR-99a通过mTOR信号通路对生理性肥大起负调节作用，这可能为压力超负荷型心力衰竭提供一种新的治疗方法。
