主动脉夹层（AD）发病机理亟待阐明，既往认为血管平滑肌细胞功能改变是AD血管重构的关键环节，而血管内皮细胞在其中的作用鲜有研究。在国家自然科学基金等资助下，我们首次发现AD患者主动脉组织miRNA表达异常，并证实miR-22对内皮细胞损伤有保护作用。故miR-22是否通过调控内皮细胞损伤参与AD血管重构？又有怎样的调控机制？本项目拟（1）收集AD患者病变形态学特征等临床资料，并结合其主动脉标本上miR-22表达与病理改变，分析miR-22及内皮细胞损伤与AD发生发展的相关性；（2）小鼠AD模型上干预miR-22，观察夹层发生率等，明确miR-22调控内皮细胞损伤在AD血管重构中的作用；（3）体外以内皮细胞及其对血管平滑肌细胞的作用为着眼点，探讨miR-22调控内皮细胞损伤在主动脉重构中的机制。本项目将可能为研究主动脉血管重构机制提供新的思路，为AD的早期防诊治提出新的靶标和策略。

The pathogenesis of aortic dissection (AD) needs to be elucidated urgently, of which the change of vascular smooth muscle cells (VSMC) and subsequent vascular remodeling have been thought as key link. However，the role of vascular endothelial cells (EC) was rarely studied in AD..Supported by the National Natural Science Foundation (finished project), our previous study has revealed for the first time the significant difference of microRNA expression between TAD patients and normal. Quantitative analysis verified miR-22 was downregulated in AD aortic tissues. Moreover, pre-experiment on zebrafish discovered that inhibition of miR-22 decreased the growth of intersegmental blood vessel and dorsal artery, which affected by the function of EC. Then, what’s the effect of miR-22 on EC in vascular remodeling of AD? What’s the regulatory mechanism involved? we design the research as follows: .Firstly, we would collect the morphological characteristics of AD and other clinical data of AD patients. Combining with the expression and detribution of miR-22 and histopathologic feature of the aortic wall tissues, we would analysize the relationship among miR-22 expression, EC injury and the process of AD pathogenesis. Secondly, in mouse AD model, we would investigate the effect of miR-22 (intervention including upregulation and downregulaion) on the severity of pathological changes, to verify the regulatory effect of miR-22 on vascular remodeling of AD. Observation indexes include the incidence of AD, histopathologic characteristics and mechanical properties of aortic wall, etc. Thridly, focusing on EC and its interaction with VSMC, we would investigate the regulatory mechanisms of miR-22 in vascular remodeling of aortic dissection by method of coculturing ex-vivo (EC cocultures with VSMC)..This study might provide new insight into the regulatory effect of microRNA on endothelial cell function in vascular remodeling of AD, and provide novel strategies of early prevention, treatment and prognostic evaluation of AD.