血管内皮细胞活化和免疫细胞粘附引起的血管炎症反应是各种血管炎性疾病如动脉粥样硬化的重要病理基础。血管细胞黏附分子1（VCAM-1）通过诱导免疫细胞向活化的内皮细胞粘附，参与多种慢性炎症的始动与发生发展。显然，靶向干预VCAM-1的表达与功能可能成为一种新的治疗方向。我们的前期研究发现，TRIM65具有E3泛素连接酶活性，并可特异性降解VCAM-1。因此，我们提出假说：TRIM65通过对VCAM-1的转录后修饰，参与免疫细胞粘附和迁移的调节，进而影响动脉粥样硬化等血管炎症疾病的转归。我们拟利用血管内皮细胞特异性TRIM65敲除小鼠和体外细胞模型深入探讨TRIM65降解VCAM-1的特异性调控机制，并阐明TRIM65介导的VCAM-1转录后修饰在白细胞粘附迁移及动脉粥样硬化发生发展过程中的作用及其机制。毋宁质疑，TRIM65作为一个全新的作用靶点在动脉粥样硬化防治中具有重要的理论和临床意义。

Vascular inflammation induced by endothelial cell activation and leukocytes adhesion is the most important pathological basis of various inflammatory diseases such as atherosclerosis. It has been reported that vascular cell adhesion molecule-1 (VCAM-1) participates in the initiation and development of varies chronic inflammation by inducing the adhesion of immune cells to activated endothelial cells. Given the importance of VCAM-1 in inflammation, intervention of the expression and function of VCAM-1 may be a possible strategy for curing vascular inflammation such as atherosclerosis clinically. Our preliminary results showed that TRIM65 might act as an ubiquitin E3 ligase to specifically degrade VACM-1. Therefore, we hypothesize that TRIM65 E3 ligase is essential to the regulation of vascular inflammation disease such as atherosclerosis by selectively targeting VCAM-1 degradation. In this study, we will explore the roles and molecular mechanisms of TRIM65 in the regulation of VCAM-1, and clarify the roles and mechanisms of TRIM65-mediated posttranscriptional modification of VCAM-1 in the regulation of leukocytes adhesion and atherosclerosis. There is no doubt that to identify TRIM65 as a new target for preventing and treating atherosclerosis will have an important significance theoretically and clinically.