微血管并发症是糖尿病患者致死致残的主要原因之一，而微血管内皮细胞通透增高以及血管新生的发生是糖尿病血管性疾病的病理生理基础，了解具体的机制很有意义。研究显示beta-catenin可能参与细胞粘附链接和细胞骨架蛋白的调节并介导VEGF与其受体表达增高促进血管新生。因此我们提出假设：在AGEs的作用下，beta-cetenin可能通过不同的磷酸化位点，一方面削弱细胞间粘附连接结构，使细胞间粘附力缩小；另一方面引起细胞骨架蛋白重塑，增加细胞的收缩力。细胞间的粘附力和细胞收缩力失衡，最终导致微血管内皮细胞屏障功能障碍以及细胞的迁移性增高。并进一步通过beta-catenin的入核作用介导基因表达，促进血管新生。拟通过beta-catenin基因敲除以及激活型或失活型过表达动物及细胞模型验证这一假说,以进一步阐明AGEs致内皮细胞通透性增高以及血管新生的作用机制。

Endothelial hyperpermeability and angiogenesis are critical events in the development of diabetic microvascular complications. Advanced glycation end products (AGEs) have been frequently suggested to cause endothelial hyperpermeability and angiogenesis associated with diabetic mellitus. Here, we aim to uncover the adversely regulation of adherence junctions during AGE-induced endothelial hyperpermeability and spotlight the phosphorylation of β-catenin in this process. We investigate whether AGEs induce β-catenin Y654 and Y142 phosphorylation to uncouple the VE-cadherin/β-catenin complex which lead to endothelial monolayer hyperpermeability and mesenteric microvascular barrier leakage. Further more we also aim to identify whether β-catenin nuclear translocation induced by AGEs could lead to angiogenesis. Taken together, our study focus on the critical role of β-catenin in AGE-mediated endothelial hyperpermeability and angiogenesis.