E-选择素和基底硬度调控中性粒细胞跨内皮迁移的力学-生物学耦合机制

项目名称： E-选择素和基底硬度调控中性粒细胞跨内皮迁移的力学-生物学耦合机制

项目编号： No.91539119

项目类型： 重大研究计划

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 章燕

作者单位： 中国科学院力学研究所

项目金额： 70万元

中文摘要： 心血管疾病包括动脉粥样硬化通常是由慢性血管炎症导致的，炎症反应贯穿于动脉粥样硬化发生和发展的整个过程。斑块能增加中性粒细胞的跨膜迁移。内皮细胞虽然是生理上的屏障，但是在和白细胞相互作用中，也通过自身细胞骨架的动态重建积极地调控白细胞跨膜迁移，而且这种调控依赖于各种生物、化学和力学环境。.本项目以血管稳态及重建为切入点，以白细胞-内皮细胞相互作用为生物学体系，采用先进的生物力学、生物材料和活细胞成像技术，着眼于动脉粥样硬化中内皮细胞微丝骨架动态重组对中性粒细胞跨膜迁移的影响，研究E-选择素和基底硬度调控中性粒细胞跨内皮迁移的力学-生物学耦合机制，深化对心血管疾病发生发展机制（尤其是动脉粥样硬化）的认识，寻找动脉粥样硬化中导致PMN过度募集的药物靶标。

中文关键词： 动脉粥样硬化；E-选择素；基底硬度；跨膜迁移；力学-生物学机制

英文摘要： Cardiovascular diseases, including atherosclerosis, represent major health problems in the human population and are caused primarily by chronic vascular inflammation. This inflammation is characterized by an increased influx of activated leukocytes, which is stimulated by stiffening of the vascular wall. But the mechanism regulating increased transmigration of neutrophil remains unclear. Upon leukocytes transmigration, it becomes increasingly evident that ECs are not only a physical barrier but that they actively support leukocytes during transmigration. One major feature of this active support is the remodeling of the endothelial actin cytoskeleton to allow for the morphological changes that enable leukocyte transmigration. And the actin dynamics are regulated possible by biological, biochemical and biomechanical environment. However, most studies focused on ICAM-1-Beta2 integrin interactions and subsequent signaling mechanisms. Few studies highlighted the importance of E-selectin and vascular stiffness on endothelial actin remodeling for leukocyte transmigration..Here, using a multidisciplinary approach, we explore the role and the underlying mechano-biological mechanisms of E-selectin and stiffness regulating PMN migration through the vascular endothelium. The study has significance for understanding the occurrence and development of cardiovascular diseases, and holds potential to intervene for prevention or attenuation of cardiovascular disease progress.

英文关键词： Atherosclerosis;E-selectin;stiffness;transmigration;mechano-biological mechanism