糖尿病加速动脉粥样硬化的分子机制尚不明了，而且缺乏相应行之有效的治疗手段。研究发现，内皮细胞向间充质细胞转分化(EndMT)参与动脉粥样硬化、糖尿病血管硬化、心脏、肾脏纤维化和癌症的发生。我们的前期研究发现高血糖可以激活PARP-1的活化参与血管EndMT，并促进动脉粥样硬化的发生。在此研究基础上，本项目提出以下研究假说：PARP-1并介导高血糖诱导主动脉EndMT，促进糖尿病动脉粥样硬化的发生、发展。为证实以上假说，本项目将以血管内皮细胞为研究对象，以高血糖诱导EndMT为切入点研究：（1）PARP-1在高血糖诱导血管EndMT与糖尿病加速动脉粥样硬化过程中的生物学功能；（2）揭示PARP-1在高血糖诱导血管EndMT与糖尿病加速动脉粥样硬化分子机制；（3）寻找PARP-1基因敲除小鼠糖尿病动脉粥样硬化模型EndMT与糖尿病加速动脉粥样硬化的病理机制和可能的治疗方法。

Vascular atherosclerosis is one of the common complecations in diabetes mellitus. Many studies have shown that high glucose caused cardiovascular atherosclerosis, but its underlying mechanisms are not fully understood. Recent evidebces have showen that the endothelial-to-mesenchymal transition could be triggered in atherosclerosis of diabetes mellitus. Our prevous research has indicated that PARP-1 is a key factor in high glucose induced EndMT in human aortic endothelial cells. Therefoe, We will address the question of PARP-1 functions in high glucose induced EndMT could be association with cardiovascular atherosclerosis in diabetes mellitus.