STRESS FAILURE AND REMODELING IN PULMONARY CAPILLARIES

肺毛细血管的应力衰竭和重塑

• 批准号: 6530704
• 负责人: JOHN B WEST
• 金额: $ 35.3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-17 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6530704
• 关键词: angiogenesis; basement membrane; blood pressure; capillary; extracellular matrix proteins; growth factor; laboratory rabbit; laboratory rat; mechanical stress; pulmonary circulation; pulmonary edema; vascular endothelium permeability

DESCRIPTION (Applicant's abstract): The long-term objective of this project is to obtain a better understanding of a new mechanism of pulmonary edema and hemorrhage, namely mechanical stress disruption of pulmonary capillaries. Pulmonary edema and is a common, serious condition and the elucidation of its mechanisms is therefore of great importance. We propose novel basic studies of the regulation of the support structures of the capillary wall, and also to continue studies of the conditions in which stress failure of the blood-gas barrier (BGB) occurs. The first group of specific aims is devoted to the regulation of the support structures of the capillary wall and includes studies of gene expression of extra cellular matrix proteins, other components of basement membranes, and growth factors in animal models where capillary wall stress is increased. These include an isolated perfused rat lung preparation where capillary wall stress is increased by raising capillary transmural pressure, or inflating the lung to high volumes. In addition we will study induced heart failure in dogs where the pulmonary capillary pressure is increased over several weeks. The second group of specific aims is devoted to conditions where the BGB fails when the capillary pressure is raised. These include the lungs of neonatal and prematurely born rabbits where the capillaries are at risk from stress failure because of the complex changes in the pulmonary circulation that occur at birth. It is possible that some cases of the infant respiratory distress syndrome are caused by stress failure of pulmonary capillaries. Our work to date on this project has been very productive. The identification of stress failure as the mechanism of pulmonary edema and hemorrhage has important clinical implications in many diseases, and it is apparently a cause of ventilator-induced lung injury. In addition, at the more basic level, this research is devoted to a fundamental bioengineering dilemma of the lung, namely, that the blood-gas barrier has to combine extreme thinness with immense strength.

描述（申请人的摘要）：该项目的长期目标是 为了更好地了解肺水肿的新机制和 出血，即肺毛细血管的机械应力破坏。 肺水肿，是一种常见的严重状况，阐明了它 因此，机制非常重要。我们提出了新的基础研究 调节毛细管壁的支撑结构，也是 继续研究血液压力故障的条件 发生障碍（BGB）。第一组具体目标是专门用于 调节毛细管壁的支撑结构，包括研究 额外细胞基质蛋白的基因表达，其他成分 地下室膜和毛细管壁的动物模型中的生长因子 压力增加。这些包括孤立的灌注大鼠肺制剂 通过增加毛细管透壁增加毛细管壁应力 压力，或使肺部充气到高体积。另外，我们将学习 诱发肺毛细管压力的狗的心力衰竭 在数周内增加。第二组的特定目标专门用于 毛细管压力升高时BGB失败的条件。这些 包括新生儿和早产兔子的肺 毛细血管因应力失败而面临风险，因为 出生时发生的肺循环。有些情况可能 婴儿呼吸窘迫综合征的作用是由 肺毛细血管。迄今为止，我们在这个项目上的工作非常 生产力。识别应力失败是肺的机制 水肿和出血在许多疾病中具有重要的临床意义，并且 显然，这是呼吸机诱导的肺损伤的原因。另外，在 更基本的水平，这项研究致力于基本的生物工程 肺部的困境，即血液屏障必须结合极端 薄，强度巨大。