Department of Vascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210000, China.
Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, China.
J Transl Med. 2019 Aug 15;17(1):270. doi: 10.1186/s12967-019-2015-z.
Deep venous thrombosis (DVT) of lower extremities is a common thrombotic disease, occurring either in isolation or as a complication of other diseases or procedures. MiR-21 is one of important microRNAs which play critical role in various cellular function. This study aim to determine the effect of miR-21 on endothelial progenitor cells (EPCs) and its role in predicting prognosis of DVT.
EPCs was isolated from DVT models and control subjects. miR-21 expression was confirmed by RT-PCR. Potential target mRNA was predicted by bioinformatics analysis. EPCs biological functions were examined by CCK-8 and tube formation assay. Besides, miR-21 expression was determined in DVT patients to investigate the correlation between miR-21 expression and prognosis of DVT. Cox proportional hazard regression analyses were also performed to reveal the risk factors associated with prognosis.
Here, we found miR-21 was downregulated in EPCs of DVT model rats. Increased miR-21 expression promoted proliferation and angiogenesis of EPCs. Moreover, we demonstrated that FASLG was a target of miR-21 and revealed that FASLG knockdown inhibited function of EPCs. Upregulation of miR-21 led to thrombus resolution in a rat model of venous thrombosis. In addition, lower expression level of miR-21 in DVT patients was associated with an increase of recurrent DVT and post thrombotic syndrome (PTS). Furthermore, Cox proportional hazard regression analyses demonstrated miR-21 expression level as an independent predictor of recurrence of DVT.
Our data revealed a role of miR-21 in regulating biological function of EPCs and could be a predictor for recurrent DVT or PTS.
下肢深静脉血栓形成（DVT）是一种常见的血栓性疾病，可单独发生，也可作为其他疾病或治疗的并发症。miR-21 是一种重要的 microRNA，在各种细胞功能中发挥关键作用。本研究旨在确定 miR-21 对内皮祖细胞（EPCs）的影响及其在预测 DVT 预后中的作用。
从 DVT 模型和对照受试者中分离 EPCs。通过 RT-PCR 证实 miR-21 的表达。通过生物信息学分析预测潜在的靶 mRNA。通过 CCK-8 和管形成测定法检查 EPCs 的生物学功能。此外，还测定了 DVT 患者的 miR-21 表达，以研究 miR-21 表达与 DVT 预后之间的相关性。还进行了 Cox 比例风险回归分析，以揭示与预后相关的危险因素。
在这里，我们发现 miR-21 在 DVT 模型大鼠的 EPCs 中下调。增加的 miR-21 表达促进了 EPCs 的增殖和血管生成。此外，我们证明 FASLG 是 miR-21 的靶标，并揭示了 FASLG 敲低抑制了 EPCs 的功能。miR-21 的上调导致静脉血栓形成大鼠模型中的血栓溶解。此外，DVT 患者中 miR-21 表达水平降低与复发性 DVT 和血栓后综合征（PTS）的增加有关。此外，Cox 比例风险回归分析表明 miR-21 表达水平是 DVT 复发的独立预测因子。
我们的数据揭示了 miR-21 在调节 EPCs 生物学功能中的作用，并且可能是复发性 DVT 或 PTS 的预测因子。
