内皮细胞(EC)损伤或功能障碍是各种心血管疾病发病机理中的初始事件。已经假定祖细胞能够分化为EC,促进内皮再生,减轻血管病理性重塑。然而,精确的细胞起源和潜在机制仍然难以捉摸。通过单细胞RNA测序(scRNA-seq),我们发现,在小鼠血管重塑过程中,表达干细胞抗原1(Sca1)的祖细胞数量增加.使用小鼠股动脉损伤和静脉移植模型,我们确定Sca1+细胞分化成ECs,在动脉和静脉重塑过程中恢复内皮。值得注意的是,我们观察到Sca1+细胞向ECs的分化受到microRNA-145-5p(miR-145-5p)-红细胞转化特异性相关基因(ERG)通路的负调控.抑制miR-145-5p促进Sca1+细胞分化并减少血管损伤后的新内膜形成。最后,与健康静脉相比,在人动静脉瘘中观察到类似的miR-145-5p下调.
Endothelial cell (EC) damage or dysfunction serves as the initial event in the pathogenesis of various cardiovascular diseases. Progenitor cells have been postulated to be able to differentiate into ECs, facilitate endothelial regeneration, and alleviate vascular pathological remodeling. However, the precise cellular origins and underlying mechanisms remain elusive. Through single-cell RNA sequencing (scRNA-seq), we identified an increasing population of progenitors expressing stem cell antigen 1 (Sca1) during vascular remodeling in mice. Using both mouse femoral artery injury and vein graft models, we determined that Sca1+ cells differentiate into ECs, restored endothelium in arterial and venous remodeling processes. Notably, we have observed that the differentiation of Sca1+ cells into ECs is negatively regulated by the microRNA-145-5p (miR-145-5p)-Erythroblast transformation-specific-related gene (ERG) pathway. Inhibiting miR-145-5p promoted Sca1+ cell differentiation and reduced neointimal formation after vascular injury. Finally, a similar downregulation of miR-145-5p in human arteriovenous fistula was observed comparing to healthy veins.