动脉粥样硬化是脑梗死的主要病理基础，单核细胞在损伤内皮局部的聚集是该炎症过程的起始反应。我们前期研究发现：ox-LDL刺激活化的内皮细胞中，miR-451表达降低，促进了单核细胞向活化内皮的趋化及粘附。且miR-451可以调控MIF及其下游趋化分子MCP-1,粘附分子ICAM-1/VCAM-1的表达。miR-451在动脉粥样硬化中如何调控单核细胞的趋化及粘附是值得研究的问题。本项目拟在细胞和动物水平上，利用 miR-451类似物/抑制物，采用病毒转染、双荧光素酶报告系统、分子生物学、免疫组化、蛋白质印迹等多种技术相结合的实验方法，阐明miR-451对动脉粥样硬化斑块形成的影响；明确 miR-451对MIF的调控作用，及其调控单核细胞向损伤内皮趋化、粘附的具体分子机制；通过对其中关键分子如miR-451、MIF等进行干预，抑制动脉粥样硬化斑块形成，为动脉粥样硬化的治疗提供新的靶点和理论基础。

Atherosclerosis is the main cause of various ischemic infarction, and the initial evidence of the inflammation is the cluster of monocytes on damaged endothelium of the artery lumen. Previous studies showed that the down-regulation of miR-451 in ox-LDL activated endothelial cells enhances monocytes’ chemotaxis and adhesion to the damaged endothelium. Our studies further proved that miR-451 can regulate MIF and its downstream chemokine MCP-1, as well as adhesion molecules ICAM-1/VCAM-1. How miR-451 regulates monocytes’ chemotaxis and adhesion in atherosclerosis is worthy to study.This project intends to conduct a cellular level study of the effect of miR-451 on the formation of atheromatous plaques, using miR-451 mimics and inhibitors, and techniques combined such as transfection, dual-luciferase reporter system, molecular biology and immunohistochemistry procedures, and Western blotting. The project also aims at investigating the regulation of miR-451 on MIF and the detailed molecular mechanism of monocytes’ chemotaxis and adhesion to the damaged endothelium. By the interference with key molecules such as miR-451 and MIF to inhibit the formation of atheromatous plaques, this study could provide theoretical basis and new target to the therapy of atherosclerosis.