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.

中文翻译：

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超声心动图检查的血浆miR-451可作为肺动脉高压的诊断参考。

由于缺乏典型的临床症状，诊断肺动脉高压（PH）的平均延迟时间超过2年。寻找用于PH诊断的生物标志物已迫在眉睫。在这项研究中，我们调查了血浆microRNA（miRNA）是否可用作PH诊断的生物标记。我们使用微阵列鉴定了PH和非PH患者之间的动态miRNA。在q小鼠模型中使用qRT-PCR对候选miRNA进行了验证，该模型是由单芥子碱（MCT）注射诱导的。我们观察到miR-21，miR-126，miR-145，miR-191和miR-150在对照小鼠和经MCT处理的小鼠之间没有差异。但2wk-MCT组的血浆miR-451显着降低，而4wk-MCT组则没有进一步降低。PH患者的血浆miR-451也明显降低，而miR-21，miR-126，miR-150和miR-320在53例PH患者和54例非PH患者之间未显示差异。根据患者数据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（AUC）分别为0.710和0.766。miR-451和D-ECHO的结合，AUC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对PH的诊断价值可与D-ECHO媲美，而miR-451与D-ECHO的组合比单独的两种方法具有更好的诊断价值，这可能对PH诊断具有影响。根据患者数据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（AUC）分别为0.710和0.766。miR-451和D-ECHO的结合，AUC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对PH的诊断价值可与D-ECHO媲美，而miR-451与D-ECHO的组合比单独的两种方法具有更好的诊断价值，这可能对PH诊断具有影响。根据患者数据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（AUC）分别为0.710和0.766。miR-451和D-ECHO的结合，AUC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对PH的诊断价值可与D-ECHO媲美，而miR-451与D-ECHO的组合比单独的两种方法具有更好的诊断价值，这可能对PH诊断具有影响。miR-451和D-ECHO的ROC曲线下面积（AUC）分别为0.710和0.766。miR-451和D-ECHO的结合，AUC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对PH的诊断价值可与D-ECHO媲美，而miR-451与D-ECHO的组合比单独的两种方法具有更好的诊断价值，这可能对PH诊断具有影响。miR-451和D-ECHO的ROC曲线下面积（AUC）分别为0.710和0.766。miR-451和D-ECHO的结合，AUC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对PH的诊断价值可与D-ECHO媲美，而miR-451与D-ECHO的组合比单独的两种方法具有更好的诊断价值，这可能对PH诊断具有影响。