血管内皮细胞糖萼是位于内皮细胞顶膜的一层绒毛状多糖蛋白复合结构，是内皮细胞表面的天然屏障。低剪切力（LSS）通过损伤血管内皮细胞糖萼促进动脉粥样硬化的形成与发展，但损伤机制不明。我们前期工作已发现LSS通过透明质酸酶2（HYAL2）途径降解细胞糖萼层透明质酸（HA），但剪切力信号如何转换为分子生物学信号并激活HYAL2并不清楚。结合相关报道和预实验结果，我们推测整合素β4（ITGβ4）是将LSS信号转换为分子生物学信号的关键分子，并通过Shc分子损伤内皮糖萼。我们用血管内皮细胞ITGβ4特异性敲除和高表达小鼠制备LSS模型，进行在体研究，人脐静脉内皮细胞和小鼠主动脉内皮细胞进行体外研究，从细胞到整体水平探索LSS损伤内皮细胞糖萼的机制，为动脉粥样硬化的防治提供新的思路和靶点。

The endothelial glycocalyx is a villous glycoprotein complex localized on the apical surface of endothelial cells and a protective barrier. Low shear stress(LSS) is correlated to generation and development of atherosclerosis through impairing the endothelial glycocalyx. However, how is glycocalyx injured by LSS remaines to be unclear. Our previous studies have found LSS activated hyaluronidase 2 (HYAL2) to degrade hyaluronan(HA) within endothelial glycocalyx. But how shear stress signal is convered to molecular biological signal to activate HYAL2 is unknown. Being based on the previous studies and the foundings in our pre-experiments, we hypothesized that integrin β4 (ITGβ4) is the key molecular for this signal converting and promotes glycocalyx impairment through Shc molecular. We are going to establish LSS model in endothelium-specific ITGβ4 knockout and over-express mice. Some studies in vitro were planed using mouse aortic endothelial cells and human umbilical vein endothelial cells. The current study will promote understanding of the mechanisms underlying the progression of LSS-induced glycocalyx impairment, and will provide new evidences and additional new clues to development of new drugs for prevention and treatment of atherosclerosis.