Regulation and function of AMPK in endothelial cells

amp活化蛋白激酶（AMPK）在内皮细胞能量供应、应激保护和维持抗炎和抗动脉粥样硬化表型中发挥作用。目前关于AMPK在内皮细胞中的调节和功能的项目将集中在两个目标上。我们将证明AMPK含有抑制性磷酸化位点的假设，并且靶向该位点可能是影响AMPK活性的一种方法。我们将进一步研究AMPK是否以及如何参与内皮屏障功能的调节，以及它如何控制内皮细胞的迁移。我们假设在低能态激活的AMPK可以保护内皮结构和连接。相反，通过受体依赖的信号通路激活的AMPK可能支持屏障破坏和细胞运动。为了验证这一假设，我们将研究AMPK刺激的不同途径的作用，表征与内皮结构调节相关的AMPK靶点，并在体外和具有基因消融的AMPK a1亚基（渗透性、迁移、血管生成）的小鼠中进行功能分析。我们期望在这个项目中获得的数据将有助于开发针对内皮功能障碍的药理学策略。

The AMP-activated protein kinase (AMPK) plays a role in endothelial cell energy supply, stress protection and maintaining an antiinflammatory and antiatherogenic phenotype. The present project on AMPK regulation and function in endothelial cells will focus on two goals. We will prove the hypothesis that AMPK contains an inhibitory phosphorylation site and that targeting this site may be an approach to affect AMPK activity. We will further investigate whether and how AMPK is involved in the regulation of endothelial barrier function and how it controls endothelial cell migration. We hypothesize that AMPK activated at low energy state will preserve endothelial structure and junctions. In contrast, AMPK activated via receptor-dependent signalling pathways may support barrier disruption and cell movement. To verify this hypothesis, we will investigate the role of different pathways of AMPK stimulation, characterize AMPK targets related to the regulation of endothelial structure and perform functional assays in vitro and in mice with genetically ablated AMPK a1 subunit (permeability, migration, angiogenesis). We expect that the data obtained in this project will contribute to the development of pharmacological strategies targeting endothelial dysfunction.