EFFECTS OF FLOW & PRESSURE ON CULTURED ENDOTHELIAL CELLS

流动的影响

• 批准号: 3337124
• 负责人: SUZANNE G ESKIN
• 金额: $ 15.75万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-05-01 至 1990-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3337124
• 关键词: antithrombogenic surface; aorta; basement membrane; biomaterial interface interaction; blood pressure; cardiovascular prosthesis; cell adhesion; cell cycle; cell growth regulation; cinemicrography; cytoskeleton; electron microscopy; extracellular matrix; fibrin; human tissue; immunofluorescence technique; inflammation; mechanical stress; neutrophil; nonelectrolyte transport; peptidyl dipeptidase A; physical model; platelets; polyurethanes; prostacyclins; radiotracer; scanning electron microscopy; tissue /cell culture; tissue support frame; tritium; vascular endothelium; vascular endothelium permeability; veins

The endothelial cells (EC) lining the blood vessels are probably involved in the etiology of all vascular disease. The fluid mechanical forces resulting from blood flow and pressure may injure the EC, but this is as yet unproven. Tissue cultured EC provide a tool to prove (or disprove) this hypothesis, by subjecting the cells to physical forces in a controlled environment. Recent studies indicate that shear stress has dramatic effects on EC structure and function. Such in vitro studies bring two problems to the forefront. First, what is the best way to simulate the mechanical forces the ED experience in vivo? Second, if mechanical stress damages EC, what constitutes "damage", short of outright detachment? We are uniquely qualified to answer these important questions. Our present system for subjecting EC to flow is capable of 1) a wide range of steady or pulsatile shear stresses (1-150 dynes/square cm), fluid dynamically well characterized, 2) continuous light microscopic videorecording, and 3) small "medium-to-cell" ratio so that cell secretions can be measured, 4) long term (5 da.) experiments. Functional and structural assays for describing EC response in this system will be prostacyclin synthesis, angiotensin converting enzyme activity, macromolecular transport changes, extracellular matrix changes, cytoskeletal changes and morphometric analysis. The effects of steady and pulsatile shear stress, cyclic substrate deformation, and substrate permeability on EC will be assessed independently. Then these factors and forces will be combined into one device which most accurately simulates the blood/vessel wall interface. With this device, interaction between polymorphonuclear leukocytes and EC will be studied as a model of the inflammatory response. Interactions between platelets and EC will be studied as a model of thrombosis. Vascular graft endothelialization will be modelled with EC interactions with fibrin and biomaterials, with particular attention to explaining the lack of endothelialization observed in man. Finally, whether vessel location in the cardiovascular system or species or origin of the vessel affect EC response to physical forces will be determined.

血管内衬的内皮细胞（EC）可能参与其中 所有血管疾病的病因学。 流体机械力 由于血流和压力可能会损害EC，但这是因为 但尚未证实。 组织培养EC提供了一种证明（或反驳） 这种假设，通过使细胞在受控的环境中受到物理力， 环境 最近的研究表明，剪切应力具有显著的 影响EC结构和功能。 这种体外研究带来了两个 把问题摆在最前沿。 首先，什么是模拟 艾德在体内经历的机械力？ 其次，如果机械应力 损害赔偿EC，什么构成“损害”，除了彻底的分离？ 我们是唯一有资格回答这些重要问题的。 我们目前 用于使EC经受流动系统能够：1）宽范围的稳定或 脉动剪切应力（1-150达因/平方厘米），流体动力学良好 特征在于，2）连续光学显微镜录像，和3）小 “培养基与细胞”的比例，以便可以测量细胞分泌物，4）长 学期（5天）实验 功能和结构分析，用于描述 EC在该系统中的反应将是前列环素合成、血管紧张素 转化酶活性，大分子转运变化，细胞外 基质变化、细胞骨架变化和形态测定分析。 的 稳定和脉动剪应力的影响，周期性基底变形， 和基质对EC的渗透性将独立评估。 然后 这些因素和力量将结合成一个装置， 精确模拟血液/血管壁界面。 有了这个装置， 将研究多形核白细胞和EC之间的相互作用， 炎症反应的模型 血小板与 EC将作为血栓形成模型进行研究。 血管移植物 内皮化将用EC与纤维蛋白的相互作用建模， 生物材料，特别注意解释缺乏 最后，血管的位置是否在人的内皮化观察。 心血管系统或血管的物种或来源影响EC 将确定对物理力的响应。