TRPC4在内皮祖细胞增殖分化及血管损伤修复中的作用

内皮祖细胞(EPCs)参与损伤血管修复过程,但调控EPCs的机制不清是限制其临床应用的瓶颈。因此，深入探讨其调控机制对防治血管损伤性疾病有重要意义。研究报道EPCs的血管修复能力与钙库操纵性钙通道（SOCs）调控的钙内流有关。我们的前期研究发现，基因干扰沉默TRPC4，EPCs的钙内流明显减少。据此，本项目提出TRPC4通过调控EPCs的钙内流，影响EPCs功能的假设。通过体外细胞培养及建立颈动脉球囊损伤模型，利用RNA干扰、基因转染、基因芯片等技术，探讨TRPC4对EPCs增殖、迁移、分化的影响及其修复损伤血管能力的关系，揭示TRPC4调节EPCs功能的机制，明确TRPC4是影响EPCs血管修复能力和治疗血管损伤性疾病的新靶点，从而为血管损伤性疾病的临床防治提供理论基础。

EPCs play a key role in repairing injured blood vessels, and their capacity to repair damaged endothelium is limited. Therefore, It is important to increase the function of EPCs in the prevention early stages of the diseases induced by vascular injury such as atherosclerosis and restenosis. Previous study suggested that Ca2+ was involved to regulate the function of EPCs. In a previous study, we showed that TRPC4, the member of SOCs, may be the key in regulating EPCs Ca2+ entry,knockdown of TRPC4 signi?cantly suppressed the Ca2+ entry of EPCs. On the basis of our previous study, we hypothesized that TRPC4 affects function of EPCs by regulating its Ca2+ entry after vascular injury . To determin the effect and mechenism of EPCs proliferation，migration,differentiation induced by TRPC4 during vascular repair, we will study it by in vitro cell culture and establishment of carotid artery balloon injury model, using RNA interference, gene transfer, gene chip technology and so on, These ?ndings will provide a new mechanism for modulating proliferation，migration, differentiation of EPCs and indicate that TRPC4 may be a new target for in ducing vascular repair by EPCs ,Which will providing a theoretical basis for clinical prevention of the diseases induced by vascular injury .