Distinct patterns of circulating microRNAs (miRNAs) were found to be involved in misguided thrombus resolution. Thus, we aimed to investigate dysregulated miRNA signatures during the acute phase of pulmonary embolism (PE) and test their diagnostic and predictive value for future diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH). Microarray screening and subsequent validation in a large patient cohort (n = 177) identified three dysregulated miRNAs as potential biomarkers: circulating miR-29a and miR-720 were significantly upregulated and miR-let7a was significantly downregulated in plasma of patients with PE. In a second validation study equal expression patterns for miR-29a and miR-let7a regarding an acute event of recurrent venous thromboembolism (VTE) or deaths were found. MiR-let7a concentrations significantly correlated with echocardiographic and laboratory parameters indicating right ventricular (RV) dysfunction. Additionally, circulating miR-let7a levels were associated with diagnosis of CTEPH during follow-up. Regarding CTEPH diagnosis, ROC analysis illustrated an AUC of 0.767 (95% CI 0.54–0.99) for miR-let7a. Using logistic regression analysis, a calculated patient-cohort optimized miR-let7a cut-off value derived from ROC analysis of ≥ 11.92 was associated with a 12.8-fold increased risk for CTEPH. Therefore, miR-let7a might serve as a novel biomarker to identify patients with haemodynamic impairment and as a novel predictor for patients at risk for CTEPH.

研究发现，循环 microRNA (miRNA) 的独特模式与错误的血栓消退有关。因此，我们的目的是研究肺栓塞 (PE) 急性期失调的 miRNA 特征，并测试其对慢性血栓栓塞性肺动脉高压 (CTEPH) 未来诊断的诊断和预测价值。微阵列筛查和随后在大型患者队列（n = 177）中的验证确定了三种失调的 miRNA 作为潜在的生物标志物：PE 患者血浆中循环 miR-29a 和 miR-720 显着上调，miR-let7a 显着下调。在第二项验证研究中，发现 miR-29a 和 miR-let7a 在复发性静脉血栓栓塞 (VTE) 或死亡的急性事件中具有相同的表达模式。 MiR-let7a 浓度与超声心动图和实验室参数显着相关，表明右心室 (RV) 功能障碍。此外，随访期间循环 miR-let7a 水平与 CTEPH 的诊断相关。关于 CTEPH 诊断，ROC 分析显示 miR-let7a 的 AUC 为 0.767 (95% CI 0.54–0.99)。使用逻辑回归分析，根据 ROC 分析计算得出的患者队列优化 miR-let7a 截止值≥11.92 与 CTEPH 风险增加 12.8 倍相关。因此，miR-let7a 可能作为一种新的生物标志物来识别血流动力学受损的患者，并作为有 CTEPH 风险的患者的新预测因子。