血管内皮功能障碍（endothelial dysfunction，ED）的重要表现之一是内皮依赖的血管舒张功能降低。已知内皮型一氧化氮合酶（endothelial nitric oxide synthase, eNOS）功能障碍是ED发生的一个关键因素。血管紧张素Ⅱ（AngⅡ）是导致ED的重要原因，AngⅡ/AT1R信号可经G蛋白依赖或非依赖的途径介导，AT1R通路激活可通过多个机制引起eNOS/NO功能障碍而导致ED发生。已表明AngⅡ/AT1R通路可使PP2A活化。本课题组前期实验结果也发现双肾一夹高血压大鼠肠系膜动脉AngⅡ/AT1R通路激活可引起PP2A活性增强、eNOS去磷酸化、eNOS/NO功能障碍。但迄今AngⅡ/AT1R通路使PP2A活性增强的机制尚不清楚，本项目拟从转录水平、翻译水平、翻译后水平研究其发生机制，并探索所涉及的信号通路，以进一步阐明AngⅡ导致ED的机制。

Endothelium exerts a number of vasoprotective effects. Many of these effects are largely mediated by endothelium-derived nitric oxide, the most potent endogenous vasodilator. Accumulating evidence suggests that endothelial dysfunction is an early marker for many cardiovascular diseases. The impairment of endothelium-dependent vasodilation caused by a loss of NO. A decline in NO availability may be caused by decreased expression of the endothelial nitric oxide synthase (eNOS). Angiontensin Ⅱ is the major bioactive peptide of the renin/angiotensin system, plays a fundamental role in controlling cardiovascular homeostasis. One of its important receptors, AT1 receptor, is G protein-coupled receptor. AT1 receptor signaling can be mediated by G protein-dependent pathway and by G-independent pathway. An increasing body of evidance sugguests that angionten Ⅱ/AT1 receptor signaling pathway which activated by multiple mechanisms contributes to the occurrence of endothelial dyfunction. Also, endothelial NADPH-oxidase-derived reactive oxygen specises (ROS) induced by angioten Ⅱ/AT1 receptor was reported to uncoupling of eNOS.It has been shown that AT1 receptor mediated-pathway activated PP2A in cardiomyocyte. Our previous experimental results also suggested that angiotensin Ⅱ/AT1 receptor pathway increased PP2A activity in two-kidney-one-clip hypertensive rats mesenteric artery, leading to eNOS dephosphorylation and decreased NO production. However, molecular mechanisms underlying AT1 receptor mediated-PP2A activation remains unclear. This project intends to explore molecular mechanism underlying PP2A regulation at transcriptional level, translational level, post-translational modulation and protein-protein interaction, and the signaling pathways may be involved in. The objective of this study is to further clarify the pathogenesis of endothelial dyfuntion induced by angioten Ⅱ through AT1 receptor.