miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN.
miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN.
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miR-217 通过靶向 PTEN 促进心脏肥大和功能障碍
DOI：
10.1016/j.omtn.2018.05.013
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发表时间：
2018-09-07
期刊：
影响因子：
--
通讯作者：
Wang DW
中科院分区：
文献类型：
--
作者：
Nie X;Fan J;Li H;Yin Z;Zhao Y;Dai B;Dong N;Chen C;Wang DW
此前，我们通过miRNA图谱分析发现，在慢性心力衰竭(CHF)患者的心脏中，miR-217的表达水平增加。本研究旨在探讨miR-217在心功能不全中的作用。采用CHF患者心脏组织标本检测miR-217的表达水平。应用9型重组腺相关病毒(RAAV9)对胸主动脉缩窄(TAC)所致心功能不全小鼠的miR-217基因表达进行干预。超声心动图和有创压力-容积分析测量心脏结构和功能。在CHF患者和TAC小鼠心脏中miR-217的表达水平均升高。在体内，miR-217的过表达加剧了压力超负荷引起的心肌肥大、纤维化和心功能障碍，而miR-217-TUD介导的miR-217下调逆转了这些影响。PTEN被预测并证实为miR-217的直接靶点，PTEN的重新表达可减轻miR-217介导的心肌肥大和心功能障碍。重要的是，心肌细胞衍生的含有miR-217的外切体在体外促进成纤维细胞的增殖。所有这些发现表明miR-217通过调节PTEN参与了心肌肥大和心肌纤维化过程，这为CHF的治疗提供了一个有前景的靶点。
Previously, we found that the miR-217 expression level was increased in hearts from chronic heart failure (CHF) patients by using miRNA profile analysis. This study aimed to explore the role of miR-217 in cardiac dysfunction. Heart tissue samples from CHF patients were used to detect miR-217 expression levels. A type 9 recombinant adeno-associated virus (rAAV9) was employed to manipulate miR-217 expression in mice with thoracic aortic constriction (TAC)-induced cardiac dysfunction. Cardiac structure and function were measured by echocardiography and invasive pressure-volume analysis. The expression levels of miR-217 were increased in hearts from both CHF patients and TAC mice. Overexpression of miR-217 in vivo aggravated pressure overload-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction, whereas miR-217-TUD-mediated downregulation of miR-217 reversed these effects. PTEN was predicted and validated as a direct target of miR-217, and re-expression of PTEN attenuated miR-217-mediated cardiac hypertrophy and cardiac dysfunction. Importantly, cardiomyocyte-derived miR-217-containing exosomes enhanced proliferation of fibroblasts in vitro. All of these findings show that miR-217 participates in cardiac hypertrophy and cardiac fibrosis processes through regulating PTEN, which suggests a promising therapeutic target for CHF.
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