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长链非编码 RNA H19、MALAT1 和 MIAT 作为急性心肌梗死诊断的潜在新型生物标志物。

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

机构信息

Xinjiang Key Laboratory of Medical Animal Model Research, Xinjiang Medical University, Urumqi, China; Department of public health, Xi'an Medical University, Xi'an, China.

Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asian, China.

出版信息

Biomed Pharmacother. 2019 Oct;118:109208. doi: 10.1016/j.biopha.2019.109208. Epub 2019 Jul 12.

Abstract

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.

摘要

在这项研究中,我们评估了外周血单核细胞(PBMC)衍生的长非编码 RNA(lncRNA)作为急性心肌梗死(AMI)生物标志物的潜力。为了评估 PBMC 衍生的 lncRNA 水平在预测 AMI 临床结局中的价值。我们使用定量 RT-PCR 测量了 132 名 AMI 患者和 104 名健康参与者 PBMC 中已知与心血管疾病相关的 10 个个体 lncRNA 的水平。对于 AMI 组,在 AMI 发作后从患者中采集血液样本。在测试的 10 个 lncRNA 中,lncRNA H19、MIAT 和 MALAT1 的 mRNA 水平在 AMI 患者中明显高于健康对照组(2.3±0.2 与 1.0±0.1,p<0.001,1.5±0.1 与 1.0±0.1,p=0.002,1.8±0.2 与 1.0±0.1,p<0.001,分别)。受试者工作特征曲线分析表明,PBMC 衍生的 H19 对 AMI 具有显著的诊断价值(AUC,0.753;95%CI,0.689˜0.817)。多变量逻辑回归分析表明,H19 是 AMI 的危险风险因素(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,与心血管危险因素呈正相关,如高密度脂蛋白(HDL)(r=-0.198,p=0.010)、脂蛋白 A(r=-0.153,p=0.049)、白细胞计数(r=0.301,p<0.001)和心脏射血分数(r=-0.157,p=0.042)。此外,lncRNA H19 与心脏生物标志物呈正相关,即肌钙蛋白 T(r=0.344,p<0.001)、肌酸激酶(r=0.261,p=0.001)和肌酸激酶同工酶 MB(r=0.24,p=0.002)。因此,PBMC 衍生的 H19、MIAT 和 MALAT1 的高表达水平可被视为 AMI 的新型生物标志物。

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