内皮祖细胞 (EPC) 在维持血管内皮完整性中发挥了重要作用。我们预实验结果证实TMEM16A是钙激活氯通道的分子基础，在成熟内皮细胞及EPC中均表达内源性TMEM16A，血管紧张素II可引起TMEM16A表达增加，干扰TMEM16A可抑制AngII 诱导的内皮细胞O2-生成，并改善AngII 诱导的高血压小鼠内皮依赖性血管舒张，提示TMEM16A参与了高血压内皮功能维护，然而该作用是否与TMEM16A调节EPC功能有关尚不清楚。在此基础上，本项目拟在TMEM16A内皮条件性敲除及高表达小鼠上建立AngII诱导的高血压模型，并提取高血压病人的外周血EPC，探讨TMEM16A对高血压EPC功能的调节作用，并通过建立颈动脉内皮损伤模型，探讨TMEM16A对EPC介导的内皮修复的作用，从氯通道这一新的角度阐明心血管疾病EPC 功能受损的机制，并为寻找防治EPC 及内皮损伤的药物新靶点提供线索。

Endothelial progenitor cells (EPC) play a significant role in re-endothelialization of injured blood vessels. Our previous study has demonstrated that TMEM16A is the molecular candidate for calcium-activated chloride channel (CaCC) and plays an important role in hypertension-induced cerebrovascular remodeling. However, whether TMEM16A is involved in the regulation of EPC function is still unclear. In our pilot study, we found that TMEM16A is expressed in both mature endothelial cells （EC）and EPC, and its expression was significantly increased by Ang II. TMEM16A knockdown inhibited AngII induced O2- production in EC, and increased the endothelial dependent vascular relaxation in aorta of Ang II infused hypertensive mice, implying a functional role of TMEM16A in endothelial function. Therefore, the objective of this project is to determine how TMEM16A would influence the EPC number and function as well as its reendothelialization capacity in both AngII-induced hypertensive mice and hypertensive patients. Our proposed research may provide new insights regarding the effects of TMEM16A in cardiovascular diseases featuring EPC dysfunction and also provide a mechanistic basis for developing new target for drug production to combat EPC damage and endothelial dysfunction in hypertension.