Institute for Translational Medicine, Qingdao University, Qingdao, China.
Affiliated Cardiovascular Hospital of Qingdao University, Qingdao University, Qingdao, China.
Clin Exp Pharmacol Physiol. 2019 Jul;46(7):635-642. doi: 10.1111/1440-1681.13094. Epub 2019 Apr 29.
This study aimed to evaluate the potential of long noncoding RNAs (lncRNAs) as biomarkers for coronary artery disease (CAD). We measured the levels of three atherosclerosis- or cardiac-related lncRNAs in peripheral blood monocyte cells (PBMCs) from 20 CAD patients and 20 non-CAD control participants using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) methods. We found that the levels of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), hypoxia-inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2) and apolipoprotein A-1 antisense RNA (APOA1-AS) were significantly increased in CAD patients (KCNQ1OT1 increased by 2.38-fold, P = 0.00042; HIF1A-AS2 increased by 2.00-fold, P = 0.0001; APOA1-AS increased by 4.52-fold, P = 0.000048). The area under the ROC curve was 0.865 for KCNQ1OT1, 0.852 for HIF1A-AS2, and 0.967 for APOA1-AS. Furthermore, the combination of lncRNAs resulted in a much higher AUC value of 0.990 for the prediction of CAD. Spearman's correlation analysis showed that APOA1-AS was positively correlated with NT-proBNP, CKMB, MYO and HsTnT, whereas HIF1A-AS2 was correlated with NT-proBNP and HsTnT. Hence, the elevation of KCNQ1OT1, HIF1A-AS2 and APOA1-AS predicts CAD and these molecules may be considered as novel biomarkers of CAD.
本研究旨在评估长非编码 RNA(lncRNA)作为冠心病(CAD)生物标志物的潜力。我们使用实时逆转录-聚合酶链反应(real-time RT-PCR)方法测量了 20 例 CAD 患者和 20 例非 CAD 对照参与者外周血单核细胞(PBMC)中三种动脉粥样硬化或心脏相关 lncRNA 的水平。我们发现,lncRNA KCNQ1 反义链/反义转录本 1(KCNQ1OT1)、缺氧诱导因子 1 ɑ 反义 RNA 2(HIF1A-AS2)和载脂蛋白 A-1 反义 RNA(APOA1-AS)在 CAD 患者中显著升高(KCNQ1OT1 增加 2.38 倍,P=0.00042;HIF1A-AS2 增加 2.00 倍,P=0.0001;APOA1-AS 增加 4.52 倍,P=0.000048)。KCNQ1OT1 的 ROC 曲线下面积为 0.865,HIF1A-AS2 为 0.852,APOA1-AS 为 0.967。此外,lncRNA 的联合预测 CAD 的 AUC 值更高,为 0.990。Spearman 相关性分析显示,APOA1-AS 与 NT-proBNP、CKMB、MYO 和 HsTnT 呈正相关,而 HIF1A-AS2 与 NT-proBNP 和 HsTnT 呈正相关。因此,KCNQ1OT1、HIF1A-AS2 和 APOA1-AS 的升高预测 CAD,这些分子可被视为 CAD 的新型生物标志物。