背景:深静脉血栓形成(DVT)是由深静脉血液凝结引起的常见血管外科疾病,主要发生在下肢。内皮祖细胞(EPCs)是一种多功能干细胞,它们是血管内皮细胞的前体。EPCs已逐渐发展成为一种有前途的治疗策略,通过各种物理和化学因素的刺激促进深静脉血栓溶解和再通。
方法:在本研究中,我们利用小鼠DVT模型,并进行了一些实验,包括qRT-PCR,蛋白质印迹,管形成,伤口愈合,Transwell分析,免疫荧光,流式细胞术分析,和免疫沉淀研究HOXD9在EPCs细胞功能中的作用。还探讨了过表达HOXD9的EPCs对DVT模型的治疗作用及其机制。
结果:过表达HOXD9显著增强EPCs的血管生成和迁移能力,同时抑制细胞凋亡。此外,结果表明,HOXD9特异性靶向HRD1启动子区并调节下游PINK1介导的线粒体自噬。有趣的是,小鼠静脉注射过表达HOXD9的EPCs促进血栓溶解和再通,显著减少静脉血栓形成。
结论:这项研究的结果表明,HOXD9在刺激内皮祖细胞血管形成中起关键作用,表明其作为DVT管理的治疗目标的潜力。
BACKGROUND: Deep vein thrombosis (DVT) is a common vascular surgical disease caused by the coagulation of blood in the deep veins, and predominantly occur in the lower limbs. Endothelial progenitor cells (EPCs) are multi-functional stem cells, which are precursors of vascular endothelial cells. EPCs have gradually evolved into a promising treatment strategy for promoting deep vein thrombus dissolution and recanalization through the stimulation of various physical and chemical factors.
METHODS: In this study, we utilized a mouse DVT model and performed several experiments including qRT-PCR, Western blot, tube formation, wound healing, Transwell assay, immunofluorescence, flow cytometry analysis, and immunoprecipitation to investigate the role of HOXD9 in the function of EPCs cells. The therapeutic effect of EPCs overexpressing HOXD9 on the DVT model and its mechanism were also explored.
RESULTS: Overexpression of HOXD9 significantly enhanced the angiogenesis and migration abilities of EPCs, while inhibiting cell apoptosis. Additionally, results indicated that HOXD9 specifically targeted the HRD1 promoter region and regulated the downstream PINK1-mediated mitophagy. Interestingly, intravenous injection of EPCs overexpressing HOXD9 into mice promoted thrombus dissolution and recanalization, significantly decreasing venous thrombosis.
CONCLUSIONS: The findings of this study reveal that HOXD9 plays a pivotal role in stimulating vascular formation in endothelial progenitor cells, indicating its potential as a therapeutic target for DVT management.