EFFECTS OF FLOW & PRESSURE ON CULTURED ENDOTHELIAL CELLS

开发有效的预防和治疗方案 心血管疾病，重要的是要了解对他的控制 血管内皮细胞的功能状态。EC是天然的 在原地受到物理力量的影响。因此，准确的角色定义 在维持正常和产生病理性EC中的体力 行为很重要。剪切力，与EC相切的力 由血液流动产生的机械力被认为是 对血管内皮损伤最大。切变中的脉动变化 作为刺激的应力不同于稳定的剪切应力是未知的。这 研究将分析适应EC对稳定的反应的机制 剪应力，并将这些与脉动剪应力的响应进行比较。 其具体目的是：1.确定EC的形态变化 粘连在剪应力作用下重塑，2.测定组成 切应力作用下肠系膜粘连斑块成分的分布 EC，3.测定子宫腔表面膜蛋白的分布 在剪应力作用下，4.确定剪应力对 使用“创伤”模型的定向迁移，5.确定肌醇 脂代谢和花生四烯酸代谢与切变有关 应激诱导EC的结构响应，以及6.比较 渗透性基质上培养的EC与EC的剪应力 在传统的基质上培养。将使用以下技术 完成特定目标；增强视频的数字分析 剪切作用下干涉反射与免疫荧光活细胞 应激，显微注射荧光标记的细胞骨架蛋白和 荧光光漂白回收掺入蛋白质，透射式 电子显微镜、放射免疫分析和荧光分光光度法。 我们基础细胞生物学和工程学研究的长期成果 将阐明内皮细胞执行其功能的机制 调节止血和血栓形成，控制血管张力和 渗透性。 EC异常可能导致动脉粥样硬化、血栓形成、止血 疾病，以及炎症、免疫反应和肿瘤的发生。 切应力如何改变内皮细胞的功能将阐明这些疾病的过程。

To develop effective preventative and therapeutic regimens for cardiovascular disease, it is important to understand control of he functional state of the vascular endothelial cells (EC). EC are naturally subjected to physical forces in situ. Thus definition of the precise roles of physical forces in maintaining normal and in producing pathological EC behavior is important. Shear stress, the force tangential to the EC resulting from blood flow is considered to be the mechanical force that is most injurious to the endothelium. Whether pulsatile variations in shear stress differ as a stimulus from steady shear stress is unknown. This research will analyze the mechanisms of adaptive EC responses to steady shear stress, and compare these with responses to pulsatile shear stress. The specific aims are to 1. Determine the morphologic changes in EC adhesions as they remodel under shear stress, 2. Determine the composition and distribution of ablumenal adhesion plaque components in shear stressed EC, 3. Determine the distribution of lumenal surface membrane proteins under shear stress, 4. Determine the effects of shear stress on directional migration using a "wound" model, 5. Determine whether inositol lipid turnover and arachidonic acid metabolism are linked to the shear stress induced structural response of EC, and 6. Compare the effects of shear stress on EC cultured on a permeable substrate to those of EC cultured on conventional substrates. The following techniques will be used to accomplish the specific aims; digital analysis of video enhanced interference reflection and immunofluorescent live cells under shear stress, microinjection of fluorescently labelled cytoskeletal proteins and fluorescence photobleach recovery of incorporated protein, transmission electron microscopy, radioimmunoassays, and spectrofluorometry. The long term results of our basic cell biological and engineering studies will elucidate the mechanisms whereby endothelium carries out its functions of modulating hemostasis and thrombosis and controlling vascular tone and permeability. EC abnormalities may contribute to atherosclerosis, thrombosis, hemostatic disorders, as well as to inflammation, immune reactivity and tumorigenesis. How shear stress alters EC function will elucidate these disease processes.