清道夫受体SR-BI是高密度脂蛋白最主要的受体，其功能影响血清HDL水平并与心血管疾病密切相关。研究发现SR-BI可能借助尚未发现的辅助蛋白调控其功能。应用最新的邻近蛋白的生物素化与质谱分析相偶联技术，我们发现氧固醇结合蛋白相关蛋白8（OSBPL-8）为可能的SR-BI辅助蛋白，共聚焦显微镜发现内皮细胞中OSBPL-8与SR-BI共定位，而且OSBPL-8 特异siRNA显著下调内皮细胞膜表面SR-BI表达水平。我们推测OSBPL-8为SR-BI的辅助蛋白并调控其在内皮细胞中的功能。本研究重点探讨：1. 验证OSBPL-8为SR-BI辅助蛋白；2. OSBPL-8对SR-BI表达及功能影响，包括对HDL的结合和摄取以及下游的信号通路影响；3. OSBPL-8对eNOS活化及内皮细胞迁移修复的影响。研究结果将有助于阐明OSBPL-8调控SR-BI功能及血脂水平和影响动脉粥样硬化的相关机制。

SR-BI is the major receptor for HDL, regulating plasma HDL-c levels and significantly related to cardiovascular disease-the leading causes of death in China and worldwide. Piles of studies are suggesting that SR-BI may have undiscovered ancillary proteins which could regulate the function of SR-BI. Identify and study these ancillary protein will help us to understand the role of SR-BI in atherosclerosis. Thus, we are searching for SR-BI associated proteins by an unbiased search-restricted enzymatic tagging coupled with mass spectrometry. Oxysterol-binding protein related protein-8, short for OSBPL-8, is found to be a possible ancillary protein for SR-BI. Following studies show that OSBPL-8 and SR-BI colocalize in endothelial cells and siRNA knock-down of OSBPL-8 significantly regulate the expression level of SR-BI in endothelial cell plasma membrane. Thus, we speculate that OSBPL-8 is an ancillary protein for SR-BI and regulate SR-BI function in endothelial cells, including SRBI expression and/or plasma translocation, downstream signaling pathway of HDL binding with SR-BI, eNOS activity and endothelial cell migration and repair. These studies will allow us to determine the roles of ancillary protein OSBPL-8 in SR-BI function and understand the underneath mechanisms.