COUP-TFII负调节动脉粥样硬化发生的作用和机制

动脉粥样硬化（AS）好发于动脉，而非静脉系统，通常认为主要与血流动力学等环境因素有关。然而环境因素主要加重AS进展，并不影响其早期发生。我们前期研究以动静脉分子特征不同为切入点，发现特异表达于静脉的表型基因COUP-TFII能负调节内皮细胞粘附和炎症分子表达、抑制内皮-单核细胞粘附。以此为基础，我们提出动静脉基因表型影响AS早期发生的研究假设。通过以动静脉内皮细胞为研究对象，利用芯片筛选等方法，探讨COUP-TFII对AS相关基因表达的转录调节并筛选其下游关键基因；以ApoE基因敲除小鼠为对象，利用动静脉互换移植模型和基因修饰等方法，观察COUP-TFII影响原位动脉及静脉移植血管AS发生的作用及对上述筛选关键基因表达的调节。本研究通过探讨静脉不易发生AS的原因，旨在阐明动脉好发AS的机制，筛选的COUP-TFII下游关键基因有望成为AS早期干预的新靶点。

Atherosclerosis generally occurs in the arterial system, rather than the venous system. It was generally thought that hemodynamic and other environmental reasons are the dominating factors of atherosclerosis. However, environmental reasons mainly influence the progress of atherosclerosis rather than atherogenesis. To date, little is known about how the inherent genes of artery and vein cells are affected by environment. COUP-TFII is thought to be the master inducer of endothelial arterio-venous fate during embryonic vascular development. Our previous study found that COUP-TFII gene is a negative regulator of endothelial cell adhesion and inflammatory molecule, inhibitor of the endothelium - monocyte adhesion, suggesting that the vein phenotypic genes of COUP-TFII may play an important negative regulatory role during atherogenesis. On this basis, we hypothesized that not only hemodynamic and environmental factors but also arteriovenous molecular table different maybe related to less prone of vein compared to artery although they both in the same vascular system. By using the isolated endothelial cells from arteries and veins as well as ApoE knock-out mice, this study aims to explore the possible molecular signaling difference regulated by COUP-TFII in arterial or venous endothelial cell and their influnce to the progress of atherosclerosis.By clarifying the role of COUP-TFII negative regulation of atherosclerosis, a new target to interrupt atherosclerosis may be established with solid theoretical basis.