EFFECTS OF FLOW & PRESSURE ON CULTURED ENDOTHELIAL CELLS

血管衬里的内皮细胞(EC)可能参与了 在所有血管疾病的病因学中。流体机械力 血液流动和压力可能会损伤EC，但这是因为 但还没有得到证实。组织培养EC提供了一种证明(或反驳)的工具 这一假说，通过让细胞受到物理力量的控制 环境。最近的研究表明，剪切应力具有显著的 对EC结构和功能的影响。这样的体外研究带来了两个 把问题摆在首位。首先，模拟的最佳方式是什么 机械力在体内对ED的体验？第二，如果机械应力 损害EC，除了彻底的超然，什么是“损害”？ 我们唯一有资格回答这些重要问题。我们的现在 用于使EC经受流动的系统能够1)大范围的稳定或 脉动剪应力(1-150dynes/平方厘米)，流体动力学良好 特征，2)连续光学显微镜录像，3)小 “培养液与细胞”的比例，这样就可以测量细胞分泌物，4)长 期限(5天)实验。用于描述的功能和结构分析 EC在这个系统中的反应将是前列环素、血管紧张素的合成 转换酶活性，大分子运输变化，胞外 基质改变、细胞骨架改变和形态计量学分析。这个 恒定和脉动剪应力、循环衬底变形、 而基质对EC的渗透性将独立评估。然后 这些因素和力量将被组合到一个设备中，其中最 精确模拟血管/血管壁界面。有了这个装置， 中性粒细胞与内皮细胞的相互作用将被研究为 炎症反应的模型。血小板和血小板之间的相互作用 EC将被作为血栓形成的模型进行研究。血管移植物 内皮化将通过EC与纤维蛋白和 生物材料，特别注意解释缺乏 在人中观察到内皮化。最后，船舶位置是否在 心血管系统或血管的种类或来源影响EC 对物理力量的反应将被确定。

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.