逆转血管内皮细胞损伤是动脉粥样硬化防治的瓶颈和难点。研究表明CAPN2可与VE-cadherin结合并水解粘附蛋白，降低血管内皮细胞间的粘连，这与内皮损伤密切相关。本项目前期研究发现，沉默CAPN2可下调Hippo通路相关基因(FRMD6、MST1/2、LATS1/2、YAP)的表达，Hippo通路可改变内皮细胞骨架调控内皮运动，进而增强内皮粘连，在内皮损伤细胞模型中也发现CAPN2对Hippo通路调控细胞粘连的作用减弱。本项目围绕CAPN2调控内皮粘连的核心问题，从分子/蛋白/细胞水平，研究CAPN2-Hippo-F-actin通路调控内皮粘连的作用。同时应用小鼠动脉粥样硬化模型，验证CAPN2-Hippo-F-actin通路可通过调控血管内皮细胞的粘连，进而逆转内皮损伤，并阐明其作用机制。本项目的实施，将有助于逆转动脉粥样硬化发生中的血管内皮损伤，为该疾病的防治提供新思路和新靶点。

Reverse of the endothelial injury is a tough topic in the field of prevention and treatment of atherosclerosis. Existing research shows that CAPN2 can bind to VE-cadherin and hydrolyze adhesion proteins, thereby reduced the adhesion between endothelial cells，and endothelial cells adhesion is closely related to endothelial injury. Our studies showed that silenced CAPN2 could down-regulate the expression of Hippo pathway genes (FRMD6, MST1/2, LATS1/2, YAP) and enhance the adhesion between endothelial cells. Hippo pathway regulated cytoskeleton and change the motility of endothelial cells. We also found that CAPN2 had a weaker effect on the Hippo pathway in the endothelial injury cell model. This project focuses on the key roles of CAPN2 on endothelial cells adhesion, exploring the effects and specific mechanism by which CAPN2-Hippo-F-actin pathway regulate endothelial cells adhesion at molecular, protein and cell level respectively. Furthermore, the mouse model of atherosclerosis will be used to verify whether and how the CAPN2-Hippo-F-actin pathway can regulate endothelial injury through affecting the endothelial cells adhesion in vivo. The implementation of this project will help to reverse the vascular endothelial cells injury in the occurrence of atherosclerosis, and provide new ideas and new targets for the prevention and treatment of the atherosclerosis.