血管内皮功能障碍(vascular endothelial dysfunction, VED)是心血管疾病重要始动因素。一氧化氮（NO）介导的蛋白质巯基亚硝基化修饰调控紊乱涉及多种疾病，其在VED中的作用有待深入研究。本课题组一直从事NO在心血管系统中的作用及机制研究。预实验显示：与正常对照组相比，高血压、动脉粥样硬化动物主动脉内总巯基亚硝基化修饰水平和分布都存在明显差异；在VED细胞模型上，biotin switch/串联质谱技术检测出可发生巯基亚硝基化修饰蛋白（如CTSB/ UCHL1）。我们拟在离体细胞及整体动物上，联合特定半胱氨酸位点突变、基因敲除、过表达等方法，鉴定在VED中发生巯基亚硝基化修饰的蛋白，探讨亚硝基化修饰对靶蛋白的功能、活性及在VED中的作用，明确靶蛋白影响内皮功能的确切作用机制及其上游调控模式。可望揭示VED新机制，为血管重构相关性疾病的防治提供新的干预靶点。

Vascular endothelial dysfunction (VED) is a significant initiating factor of vascular disease. The dysregulation of protein s-nitrosylation modification mediated by nitric oxide (NO) relates to the development of various diseases, and the effect of which in VED still needs to be further studied. Our group has been engaged in studying the effect and mechanism of NO in cardiovascular system. Our prior experiments have showed that both the level and distribution of s-nitrosylated proteins have obviously difference in aorta of hypertensive or atherosclerotic rodent models compared with control. We also detected some target proteins, such as CTSB and UCHL1, can be nitrosylated in VED cell models by Biotin switch/tandem mass spectrometry. Therefore, we plan to use specific cysteine mutation, knockout and gene overexpression to not only identify the nitrosylated target proteins, but also discuss the specific effect of s-nitrosylation on protein function and activity in VED. Furthermore, we will confirm the definite mechanism and explore the upstream regulation pathway on which s-nitrosylated target proteins can affect endothelial function in vitro and vivo. This research would hopefully uncover the novel mechanism of endothelial dysfunction and provide novel targets for preventing vascular remodeling-related diseases.