Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (mainland).
Med Sci Monit. 2018 Feb 15;24:951-960. doi: 10.12659/msm.906116.
BACKGROUND Endothelial progenitor cells (EPCs) were found to be a potential therapeutic choice for low extremity deep vein thrombosis. The aim of our research was to investigate the effect of resveratrol (RSV) on EPCs that may promote thrombus resolution and its potential pathway. MATERIAL AND METHODS EPCs were pretreated with RSV and migration; angiogenesis were evaluated ex vivo. Expression of miR-138 and focal adhesion kinase (FAK) was also tested. A murine model of venous thrombosis was developed as an in vivo model. The effects of RSV treatment on mice with inferior venous thrombosis were evaluated. RESULTS We found that RSV increased EPCs migration and tube formation ex vivo. RSV significantly inhibited miR-138 expression. Moreover, we demonstrated that FAK was a target of miR-138 and revealed that FAK knockdown downregulated migration and angiogenesis of RSV-treated EPCs. In addition, RSV-induced EPCs promoted thrombus resolution in a murine model of venous thrombosis. CONCLUSIONS We found the first evidence that intravenous injection of RSV-treated EPCs enhanced thrombus resolution in vivo. RSV exerted its role by reducing miR-138 expression and therefore upregulated FAK.
内皮祖细胞(EPCs)被发现是治疗下肢深静脉血栓的一种有潜力的治疗选择。我们的研究目的是探讨白藜芦醇(RSV)对可能促进血栓溶解的 EPCs 的影响及其潜在途径。
EPCs 用 RSV 预处理,然后评估迁移和血管生成。还检测了 miR-138 和黏着斑激酶(FAK)的表达。建立了静脉血栓形成的小鼠模型作为体内模型。评估 RSV 处理对下腔静脉血栓形成小鼠的影响。
我们发现 RSV 增加了 EPCs 的体外迁移和管状形成。RSV 显著抑制了 miR-138 的表达。此外,我们证明 FAK 是 miR-138 的靶标,并揭示了 FAK 敲低下调了 RSV 处理的 EPCs 的迁移和血管生成。此外,RSV 诱导的 EPCs 促进了静脉血栓形成小鼠模型中的血栓溶解。
我们首次发现静脉注射 RSV 处理的 EPCs 可增强体内血栓溶解。RSV 通过降低 miR-138 的表达从而上调 FAK 发挥作用。