研究表明lncRNA与心血管疾病的发生发展相关，但其对AS影响的研究才刚起步。为了研究lncRNA在AS发生发展中的作用，我们通过基因芯片发现人动脉内膜斑块中lncRNA RP11-463O9.5和FOXC2的表达较人正常动脉内膜中的表达降低。生物信息学分析显示RP11-463O9.5与FOXC2位于同一染色体。预实验结果表明RP11-463O9.5能上调FOXC2的表达，且RP11-463O9.5和FOXC2都能促进细胞内胆固醇流出。因此我们提出RP11-463O9.5可能通过调节FOXC2表达从而调节胆固醇平衡进而影响AS形成。本项目拟通过增强RP11-463O9.5和/或FOXC2的表达，观察RP11-463O9.5-FOXC2对胆固醇平衡和AS形成的影响并探讨相关机制，为确定RP11-463O9.5-FOXC2作为调控胆固醇平衡和防治AS新靶点提供科学依据。

Accumulated evidences show that lncRNAs play an essential role in cardiovascular diseases. However, the effect of lncRNAs on atherosclerosis has not been fully explored. To investigate possible changes in lncRNA expression during atherosclerosis formation, we performed microarray analysis of normal arterial intima and advanced atherosclerotic plaque. The microarray analysis revealed that expression of both lncRNA RP11-463O9.5 and FOXC2 were significantly down-regulated in advanced atherosclerotic plaque when compared with control. Furthermore, bioinformatic analysis showed that the RP11-463O9.5 and FOXC2 were located in the same chromosome. Moreover, FOXC2 expression was enhanced by overexpression of RP11-463O9.5 in macrophages. In addition, cholesterol efflux was enhanced by both RP11-463O9.5 overexpression and FOXC2 overexpression in macrophages. Thus, we hypothesized that atherosclerosis development could be affected by RP11-463O9.5-FOXC2 through regulating cholesterol homeostasis. In this project, we aim to explore the effect and mechanism of RP11-463O9.5-FOXC2 pathway on cholesterol balance and atherosclerosis development by overexpression of RP11-463O9.5 and/or FOXC2. Therefore, our study may provide new scientific evidence to establish RP11-463O9.5-FOXC2 as a new target for regulation of cholesterol homeostasis and prevention of atherosclerosis.