血流剪切力参与调节血管稳态，在动脉血管分叉或弯曲处发生的湍流可引起内皮功能紊乱，具有促动脉粥样硬化的作用。而湍流引起内皮激活的内源性保护机制有待探究。作为多种心血管疾病的重要保护因子，软骨寡聚基质蛋白COMP是否影响湍流引起的内皮激活及其潜在作用机制尚未阐明。前期工作基础中我们发现COMP可抑制湍流引起的内皮激活标志物VCAM-1和ICAM-1的表达；同时免疫共沉淀实验筛选到COMP可与整合素α5结合。因此，我们的科学假说为：COMP可通过细胞外基质信号通路与integrinα5相互作用，调控其下游基因FAK的磷酸化，抑制湍流引起的内皮激活进而抑制动脉粥样硬化。拟将以COMP-integrinα5通路为中心，运用生化、细胞及分子生物学手段和基因工程小鼠，重点研究在内皮细胞中COMP抑制湍流引起的内皮激活的具体分子机制。以期为干预动脉粥样硬化早期病变的药物筛选提供理论及实验依据。

Hemodynamic shear stress is involved in regulating vascular homeostasis. Atherosclerosis occurs mainly near branches and the lesser curvature of the aortic arch where the flow is disturbed. Currently, little is known about the physiological mechanisms protecting vasculature against disturbed flow- induced endothelial cell (EC) activation. Cartilage oligomeric matrix protein (COMP), has diverse protective roles in the cardiovascular system. However, whether COMP could protect against disturbed flow-activated EC and the molecular mechanism is still unclear. Our previous study demonstrated that purified COMP inhibited EC activation caused by OSS. Co-immunoprecipitation results suggest that COMP bound directly to integrin α5. The hypothesis this project is that COMP fine-tunes disturbed flow-induced EC activation and atherosclerosis pathogenesis by interacting with integrin α5 and suppressing integrin α5 receptor pathway. With COMP-α5 cascade as a central, using biochemistry, cell and molecular biology tools and genetically engineered mice, we will investigate the molecular mechanism of COMP protect against disturbed flow-activated ECs to provide theoretical and experimental evidence for early intervention of atherogenesis.