内皮祖细胞（EPC）的数目和功能对维持血管内皮完整性发挥了重要作用。我们以往研究证明ClC-3氯通道参与了高血压血管重构及内皮功能不全的调节， 然而，ClC-3 是否参与了高血压状态下EPC的功能调节尚不清楚。我们的预实验结果证实 Ang II 能够使小鼠EPC中ClC-3的蛋白表达明显增加，ClC-3基因敲除能够显著抑制AngII 诱导的EPC凋亡，并使EPC中NADPH 氧化酶活性降低及O2-生成减少。在以上研究的基础上，本项目拟利用ClC-3 基因敲除小鼠，将离体细胞实验与整体实验相结合，从分子和离子通道水平研究ClC-3 对高血压 EPC氧化应激水平及EPC 数目和功能的调节作用及可能机制。 为进一步阐明心血管疾病中EPC功能受损的机制,并寻找防治EPC受损的新药新靶点提供实验依据。

Endothelial progenitor cells (EPC) play a significant role in neovascularization of ischemic tissues and in re-endothelialization of injured blood vessels. Our previous study has demonstrated that ClC-3 chloride channel is involved in vascular remodeling and endothelial dysfunction during hypertension. However, whether ClC-3 channel participates in the regulation of EPC function is still unclear. In our pilot study, we found that the expression of ClC-3 protein was significantly increased in Ang II-treated EPCs. Ang II treatment induced apparent EPC apoptosis, which was significantly inhibited by ClC-3 gene knockout. Furthermore, NADPH oxidase activity, as well as O2- level, was significantly lower in EPC from ClC-3 knockout mice than that from wild-type mice after Ang II administration. Therefore, the objective of this project is to determine how ClC-3 deficiency would influence the EPC number and function and the underlying mechanisms in both AngII-induced and DOCA-salt hypertension. Our proposed research may provide new insights regarding the effects of ClC-3 in cardiovascular diseases featuring EPC dysfunction and also provide a mechanistic basis for developing new target for drug production to combat EPC damage in hypertension.