Tang Yaoping, Wang Yongchao, Park Kyoung-Mi, Hu Qiuping, Teoh Jian-Peng, Broskova Zuzana, Ranganathan Punithavathi, Jayakumar Calpurnia, Li Jie, Su Huabo, Tang Yaoliang, Ramesh Ganesan, Kim Il-Man
Vascular Biology Center, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA.
Vascular Biology Center, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University CB-3717, 1459 Laney Walker Blvd, Augusta, GA, USA
Cardiovasc Res. 2015 Jun 1;106(3):387-97. doi: 10.1093/cvr/cvv121. Epub 2015 Mar 30.
Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs). For example, miR-150 is down-regulated in patients with acute myocardial infarction, atrial fibrillation, dilated and ischaemic cardiomyopathy as well as in various mouse heart failure (HF) models. Circulating miR-150 has been recently proposed as a better biomarker of HF than traditional clinical markers such as brain natriuretic peptide. We recently showed using the β-arrestin-biased β-blocker, carvedilol that β-arrestin1-biased β1-adrenergic receptor cardioprotective signalling stimulates the processing of miR-150 in the heart. However, the potential role of miR-150 in ischaemic injury and HF is unknown.
Here, we show that genetic deletion of miR-150 in mice causes abnormalities in cardiac structural and functional remodelling after MI. The cardioprotective roles of miR-150 during ischaemic injury were in part attributed to direct repression of the pro-apoptotic genes egr2 (zinc-binding transcription factor induced by ischaemia) and p2x7r (pro-inflammatory ATP receptor) in cardiomyocytes.
These findings reveal a pivotal role for miR-150 as a regulator of cardiomyocyte survival during cardiac injury.
心脏损伤伴随着微小RNA（miR）表达的动态变化。例如，在急性心肌梗死、心房颤动、扩张型和缺血性心肌病患者以及各种小鼠心力衰竭（HF）模型中，miR-150表达下调。最近有人提出，循环miR-150作为HF的生物标志物比传统临床标志物如脑钠肽更好。我们最近使用β-抑制蛋白偏向性β受体阻滞剂卡维地洛表明，β-抑制蛋白1偏向性β1肾上腺素能受体心脏保护信号刺激心脏中miR-150的加工。然而，miR-150在缺血性损伤和HF中的潜在作用尚不清楚。
在此，我们表明小鼠中miR-150的基因缺失会导致心肌梗死后心脏结构和功能重塑异常。miR-150在缺血性损伤期间的心脏保护作用部分归因于对心肌细胞中促凋亡基因egr2（缺血诱导的锌结合转录因子）和p2x7r（促炎ATP受体）的直接抑制。
这些发现揭示了miR-150作为心脏损伤期间心肌细胞存活调节因子的关键作用。
