Department of Cardiology, Changhai Hospital, Shanghai, 200433, China.
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences & Shanghai Jiao-Tong University School of Medicine, Chinese Academy of Sciences, Shanghai, 200031, China.
Acta Pharmacol Sin. 2018 Jul;39(7):1208-1216. doi: 10.1038/aps.2018.39. Epub 2018 May 24.
Due to the lack of typical clinical symptoms, the average delay time for diagnosis of pulmonary hypertension (PH) is longer than 2 years. It is urgent to find biomarkers for PH diagnosis. In this study we investigated whether plasma microRNAs (miRNAs) can be used as biomarkers for PH diagnosis. We used microarray to identify dynamic miRNAs between PH and non-PH patients. The candidate miRNAs were verified using qRT-PCR in a mouse model of PH, which was induced by monocrotaline (MCT) injection. We observed that miR-21, miR-126, miR-145, miR-191 and miR-150 had no differences between control mice and MCT-treated mice; but plasma miR-451 was significantly decreased in the 2wk-MCT group, with no further decrease in the 4wk-MCT group. Plasma miR-451 was also markedly decreased in PH patients, whereas miR-21, miR-126, miR-150 and miR-320 did not show differences between 53 PH patients and 54 non-PH patients. Receiver operating characteristic curves (ROCs) were constructed from the patient data to assess the clinical diagnostic values of circulating miR-451 and Doppler echocardiography (D-ECHO). The areas under the curve (AUCs) of ROCs for miR-451 and D-ECHO were 0.710 and 0.766, respectively. Combination of miR-451 and D-ECHO with AUC of 0.825 was superior to the use of either miR-451 or D-ECHO alone for PH diagnosis. In conclusion, plasma miR-451 has a moderate diagnostic value in PH comparable to that of D-ECHO, and the combination of miR-451 with D-ECHO has better diagnostic value than either method alone, which may have implications for PH diagnosis.
由于缺乏典型的临床症状,肺动脉高压(PH)的平均诊断延迟时间超过 2 年。因此,迫切需要寻找用于 PH 诊断的生物标志物。在本研究中,我们研究了血浆 microRNAs(miRNAs)是否可用于 PH 诊断的生物标志物。我们使用微阵列技术鉴定 PH 患者和非 PH 患者之间的动态 miRNA。在由单剂量野百合碱(MCT)注射诱导的 PH 小鼠模型中,使用 qRT-PCR 验证候选 miRNA。我们观察到 miR-21、miR-126、miR-145、miR-191 和 miR-150 在对照小鼠和 MCT 处理的小鼠之间没有差异;但是血浆 miR-451 在 2 周 MCT 组中明显降低,在 4 周 MCT 组中没有进一步降低。血浆 miR-451 在 PH 患者中也明显降低,而 miR-21、miR-126、miR-150 和 miR-320 在 53 名 PH 患者和 54 名非 PH 患者之间没有差异。从患者数据中构建接收器工作特征曲线(ROC),以评估循环 miR-451 和多普勒超声心动图(D-ECHO)的临床诊断价值。miR-451 和 D-ECHO 的 ROC 曲线下面积(AUCs)分别为 0.710 和 0.766。miR-451 和 D-ECHO 的 AUC 联合为 0.825,优于单独使用 miR-451 或 D-ECHO 进行 PH 诊断。总之,血浆 miR-451 在 PH 中的诊断价值与 D-ECHO 相当,miR-451 与 D-ECHO 的联合使用比单独使用任何一种方法具有更好的诊断价值,这可能对 PH 诊断具有重要意义。