Long non-coding RNAs H19, MALAT1 and MIAT as potential novel biomarkers for diagnosis of acute myocardial infarction

Long non-coding RNAs H19, MALAT1 and MIAT as potential novel biomarkers for diagnosis of acute myocardial infarction
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长链非编码 RNA H19、MALAT1 和 MIAT 作为诊断急性心肌梗死的潜在新型生物标志物

DOI:
10.1016/j.biopha.2019.109208
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发表时间:
2019-10-01
影响因子:
7.5
通讯作者:
Yang, Yi-Ning
Yang, Yi-Ning
中科院分区:
医学2区
文献类型:
--
作者:
Wang, Xue-Mei;Li, Xiao-Mei;Yang, Yi-Ning

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在这项研究中,我们评估了外周血单核细胞(PBMC)来源的长链非编码RNA(lncRNA)作为急性心肌梗死(AMI)生物标志物的潜力。探讨外周血单个核细胞来源的lncRNA水平在预测急性心肌梗死患者临床预后中的价值。我们使用定量RT-PCR测量了来自132名AMI患者和104名健康参与者的PBMC中已知与心血管疾病相关的10种单个lncRNA的PBMC衍生水平。AMI组于AMI发病后采集血样。在检测的10种lncRNA中,AMI患者lncRNA H19、MIAT和MALAT 1的mRNA水平显著高于健康对照组(分别为2.3 +/- 0.2对比1.0 +/- 0.1,p < 0.001,1.5 +/- 0.1对比1.0 +/- 0.1,p = 0.002,1.8 +/- 0.2对比1.0 +/- 0.1,p < 0.001)。受试者工作特征曲线分析显示,H19对AMI有显著的诊断价值(AUC,0.753,95%CI,0.689 ± 0.817),多因素Logistic回归分析显示,H19是AMI的危险因素(OR = 2.498,95%CI,1.321-4.726,p = 0.005)。此外,lncRNA H19的改变与许多心血管保护因素呈负相关,与心血管危险因素如高密度脂蛋白(HDL)呈正相关。(r =-0.198,p = 0.010)、脂蛋白A(r =-0.153,p = 0.049)、白色细胞计数(r=0.301,p < 0.001)和心脏射血分数(r =-0.157,p = 0.042)。此外,lncRNA H19与心肌生物标志物肌钙蛋白T(r = 0.344,p < 0.001)、CK(r=0.261,p = 0.001)和CKMB(r = 0.24,p = 0.002)呈正相关,提示H19、MIAT和MALAT 1表达水平升高可能是AMI的新的生物标志物。
In this study, we evaluated the potential of peripheral blood mononuclear cells (PBMC) derived long non-coding RNAs (lncRNAs) as biomarkers for acute myocardial infarction (AMI). To assess the value of PBMCs-derived lncRNAs levels in predicting clinical outcomes in AMI. We measured the PBMC-derived levels of 10 individual lncRNAs which are known to be relevant to cardiovascular disease in PBMCs from 132 AMI patients and 104 healthy participants using quantitative RT-PCR. For AMI group, blood sample were obtained from patients after the onset of AMI. Out of the 10 lncRNAs tested, the mRNA level of lncRNA H19, MIAT and MALAT1 were significantly higher in AMI patients than in healthy control (2.3 +/- 0.2 vs. 1.0 +/- 0.1, p < 0.001, 1.5 +/- 0.1 vs. 1.0 +/- 0.1, p = 0.002, 1.8 +/- 0.2 vs. 1.0 +/- 0.1, p < 0.001, respectively). Receiver operating characteristic curve analyses showed that PBMC-derived H19 had significant diagnostic value for AMI (AUC, 0.753; 95% CI, 0.689 0.817).Multivariate logistic regression analysis showed that H19 as a dangerous risk for AMI (OR = 2.498, 95% CI, 1.321-4.726, p = 0.005). In addition, the lncRNA H19 alteration was inversely associated with a number of cardiovascular protective factors, and positively associated with cardiovascular risk factors, such as high-density lipoprotein (HDL) (r = -0.198, p = 0.010), lipoprotein A (r = -0.153, p = 0.049), white blood cell counting (r=0.301, p < 0.001) and cardiac ejection fraction (r = -0.157, p = 0.042). Moreover, lncRNA H19 was positively correlated with cardiac biomarkers, i.e. troponinT (r = 0.344,p < 0.001), CK (r=0.261, p = 0.001) and CKMB (r = 0.24, p = 0.002).Hence, elevated expression level of PBMC-derived H19, MIAT and MALAT1 may be considered as novel biomarkers of AMI.