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线粒体长链非编码RNA作为肥厚型心肌病患者心脏重塑的血液生物标志物

Mitochondrial long noncoding RNAs as blood based biomarkers for cardiac remodeling in patients with hypertrophic cardiomyopathy.

作者信息

Kitow Janina, Derda Anselm A, Beermann Julia, Kumarswarmy Regalla, Pfanne Angelika, Fendrich Jasmin, Lorenzen Johan M, Xiao Ke, Bavendiek Udo, Bauersachs Johann, Thum Thomas

机构信息

Institute of Molecular and Translational Therapeutic Strategies (IMTTS), IFB-Tx, Hannover Medical School, Hannover, Germany;

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany; and.

出版信息

Am J Physiol Heart Circ Physiol. 2016 Sep 1;311(3):H707-12. doi: 10.1152/ajpheart.00194.2016. Epub 2016 Jul 15.

Abstract

Hypertrophic cardiomyopathy (HCM) is a hereditary heart disease with a high risk for sudden cardiac death in young people. As a subtype, hypertrophic obstructive cardiomyopathy (HOCM) additionally has a left ventricular outflow gradient, showing stronger symptoms and requires a different treatment compared with hypertrophic nonobstructive cardiomyopathy (HNCM). In this study our aim was to investigate the regulation of mitochondrial and cardiac remodeling associated long noncoding RNAs (lncRNAs) in blood of patients affected with HOCM and HNCM. We included 28 HNCM, 57 HOCM, and 26 control inviduals. Already known mitochondrial and cardiac remodeling associated lncRNAs uc004cos.4, uc004coz.1, uc004cov.4, uc011mfi.2, uc022bqw.1, uc022bqs.1, and uc022bqu.1 were amplified in serum of these patients and correlated with clinical parameters. Long noncoding RNAs uc004cov.4 and uc022bqu.1 were significantly increased in patients with HOCM but not in patients with HNCM. With the use of receiver operator characteristic (ROC) curve analysis, lncRNAs uc004cov.4 and uc022bqu.1 were able to identify HOCM patients. In our study we evidenced that the specific mitochondrial long noncoding RNAs uc004cov.4 and uc022bqu.1 were upregulated in patients with HOCM and they were also able to identify HOCM and could be developed as useful clinical biomarkers in the future.

摘要

肥厚型心肌病(HCM)是一种遗传性心脏病,在年轻人中具有较高的心源性猝死风险。作为一种亚型,肥厚型梗阻性心肌病(HOCM)还存在左心室流出道梯度,症状更为明显,与肥厚型非梗阻性心肌病(HNCM)相比,治疗方法也有所不同。在本研究中,我们的目的是调查HOCM和HNCM患者血液中线粒体及心脏重塑相关长链非编码RNA(lncRNA)的调控情况。我们纳入了28例HNCM患者、57例HOCM患者和26例对照个体。已知的线粒体及心脏重塑相关lncRNA,即uc004cos.4、uc004coz.1、uc004cov.4、uc011mfi.2、uc022bqw.1、uc022bqs.1和uc022bqu.1,在这些患者的血清中得到扩增,并与临床参数相关联。lncRNA uc004cov.4和uc022bqu.1在HOCM患者中显著升高,但在HNCM患者中未升高。通过使用受试者工作特征(ROC)曲线分析,lncRNA uc004cov.4和uc022bqu.1能够识别HOCM患者。在我们的研究中,我们证明了特定的线粒体长链非编码RNA uc004cov.4和uc022bqu.1在HOCM患者中上调,它们还能够识别HOCM,并且未来有可能被开发为有用的临床生物标志物。

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