单核细胞侵袭血管内皮层进人内膜最终形成泡沫细胞是动脉粥样硬化病变形成早期事件之一。该过程有多种糖蛋白参与，但机制尚不清楚。本项目以血管内皮细胞为研究对象，以2,6-唾液酸转移酶1（ST6Gal-1）是否通过催化VE-Cadherin唾液酸化发挥其在细胞间紧密连接的作用，而BACE1蛋白降解途径对ST6Gal-1可能起调控作用为研究核心，探讨细胞粘联的分子机制，寻找炎症诱发动脉粥样硬化的分子基础。通过建立ST6Gal-1、BACE1等基因shRNA或过表达质粒转染模型，采用qPCR、western blot、SNA/MAA blot、免疫共沉淀技术、流式细胞术和激光共聚焦显微镜等技术,检测IL-1、TNF-α诱导前后细胞中唾液酸化和粘附功能的差异，及对SphK/S1P信号通路的影响，并在动物模型上进行验证。以期回答糖基转移酶是如何影响动脉硬化形成这一科学问题，为相关疾病的防治提供新的思路。

The process of leukocyte extravasation, a critical step in the inflammatory response to form the foam cells, involves the disease from initial stage of atherosclerosis.More and more glycoproteins take part in this process. But the mechanisms have remained unclear. In the present study, the vascular endothelial cells as issue will be investigated to understand whether 2,6-sialic acid transferase 1(ST6Gal-1) can act on cell adhesion junctions via add sialic acids to VE-Cadherin and if BACE1 protein degrading pathway can down-regulation of ST6Gal-1 which may be a critical regulation mechanism. We want to know the molecular mechanism of interaction of cell to cell and find out the molecular basis of initial onset about atherosclerosis induced by inflammation. We would build up the cell models of siRNA and overexpression about ST6Gal-1、BACE1 etc. gene, useing qPCR,western blot,SNA/MAA blot, Coimmunoprecipitation, flow cytometry and confocal system to assay different levels of sialic acid on glycoprotein and adhesion function between cells treated and untreated by IL-1、TNF-α. We will perform to effect on SphK/S1P signaling pathway undergoing inflammation. We will also test in mouse model in vivo. We hope what we get from the study will answer this question: how glycosyltransferase influence onset of atherosclerosis. It will be new insights for preventing the disease of vascular inflammation.