血脂控制后动脉粥样硬化（AS）导致的终点事件残余风险仍高达70%，单纯降脂策略面临巨大挑战。中药活性成分红景天苷对AS疗效已获得广泛证实，但其作用机制尚不明确。单核-内皮细胞粘附是AS早期病理机制中关键环节，课题组前期研究表明红景天苷可通过下调NF-κB通路介导的VCAM-1表达进而抑制单核-内皮细胞粘附作用。结合前期研究基础及生物信息学分析结果，我们提出假说：红景天苷可通过直接作用于I2PP2A-PP2Ac轴，抑制p65转录因子活性，在抑制p65调控的VCAM-1转录同时还可通过CSN5介导的GATA-2去泛素化作用与GATA-2形成crosstalk机制，从而达到对VCAM-1基因转录的双重阻断作用。本项目拟运用Co-IP、ChIP、GST pull down、BiFC等试验探究红景天苷对单核-内皮细胞粘附的影响机制，为抗AS中药新药研发提供理论基础，发现潜在的抗AS治疗新靶点。

Lipid regulation still leaves 70% morbidity for atherosclerosis triggered endpoint, that challenges our existing therapeutic regimen. The outstanding effect of Salidroside on anti- atherosclerosis has been widely confirmed while its mechanism is still elusive. Monocyte-endotheliocyte adhesion has been considered to play a pivotal role in the early phase of atherosclerotic pathologic process. And we have found that Salidroside inhibit monocyte-endotheliocyte adhesion via downregulation NF-κB pathway modelated adhesion molecule expression in endotheliocytes. Based on the results from our previous research and bioinformatics analysis, we hypothesized that Salidroside blocks p65 modulated specific gene transcription via interacting with I2PP2A-PP2Ac axis, that not only gets in the way of VCAM-1 transcription and expression but also diminishes CSN5 transcription. Resultant low expression of CSN5 leads to a weak deubiquitinoylation of GATA-2, which in turn further suppresses VCAM-1 transcription. In the present study, Co-IP, ChIP, GST pull down, EMSA, TOP-Flash, western blot and BiFC are applied to investigate the mechanism underlying Salidroside triggerd inhibitory action in monocyte-endotheliocyte adhesion. Unveiling the crosstalk between NF-κB pathway and CSN5 modulated GATA-2 deubiquitinoylation is conducive to our understanding of monocyte-endotheliocyte adhesion, that offers us a new perspective to discover anti- atherosclerosis drugs.