Physiological Consequences of Hypoxia and Lung Disease

缺氧和肺部疾病的生理后果

• 批准号: 7113849
• 负责人: PETER D WAGNER
• 金额: $ 60.91万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-20 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7113849
• 关键词: biological signal transduction; chronic obstructive pulmonary disease; exercise; free radical oxygen; gene deletion mutation; gene expression; hypoxia; hypoxia inducible factor 1; inflammation; laboratory mouse; lung disorder; lung transplantation; muscle function; nitric oxide; physiologic stressor; vascular endothelial growth factors; vasodilation

DESCRIPTION: The most important consequence of lung disease is hypoxemia resulting in impaired oxygen supply to thetissues, diminishing organ function. This research program continues its commitment to understanding the causes and effects of hypoxemia in health and disease. Three of the five projects address this at the level of the skeletal muscles. A fourth deals with cardiac consequences of hypoxia, and a fifth with neural plasticity in hypoxia. The same five project'leadersare proposed as in the current cycle (years 26-30), lending continuity to a productive program. However, experimental approaches have evolved to focus more onfundamental mechanisms of the hypoxic response. Yet there are also studies proposed to link these back to humans as a function of age and disease, making for an integrated approach to the problem of hypoxia. Project 1 (Wagner) focuses on the basic molecular mechanisms of muscle angiogenesis in response to hypoxia in health and disease; Project 2 (Mathieu-Costello) uses modern morphometric methods to assess regional myocardialOz availability and the impact of chronic hypoxia and aging on this; Project 3 (Richardson) examines the effects of aging on human muscle structure and function using integrative methods ranging from macroscopic imaging to molecular biological; Project 4 (Powell) addresses the effects of hypoxia on neural function involved in ventilatory control, integrating molecular and physiological tools; Project 5 (Hogan) investigates the role of Oaavailability on single muscle fiber function in vitro using a combination of imaging, functional, and molecular methods. The projects interact extensively,many formally asjoint efforts between project leaders with overlapping interests, and are supported by three cores (Tissue Imaging and Morphometry; Molecular Biology; Administration). Our collective goals are to better understand how Oatransport between the environment and the mitochondria of several key organs is regulated as a function of aging and disease, and in turn, how hypoxia itself modulates its own availability and thereby affects organ function in these same conditions.

产品说明：肺部疾病最重要的后果是低氧血症，导致组织供氧受损，降低器官功能。这项研究计划继续致力于了解 原因和影响低氧血症的健康和疾病。五个项目中有三个在以下层面解决这一问题： 骨骼肌第四篇涉及缺氧对心脏的影响，第五篇涉及缺氧对神经的可塑性。 缺氧与本周期（第26-30年）相同的五个项目领导人被提议， 一个富有成效的计划。然而，实验方法已经发展到更加关注基础， 低氧反应的机制。然而，也有研究提出将这些与人类联系起来， 年龄和疾病的功能，使缺氧问题的综合方法。项目1（瓦格纳） 专注于肌肉血管生成的基本分子机制，以应对健康缺氧， 项目2（Mathieu-Costello）使用现代形态测量方法评估局部心肌 可用性和慢性缺氧和衰老对此的影响;项目3（理查森）研究了影响 研究衰老对人体肌肉结构和功能的影响 从影像学到分子生物学;项目4（Powell）阐述了缺氧对神经功能的影响 参与阐明控制，整合分子和生理工具;项目5（霍根）调查 利用成像，功能， 和分子方法。这些项目广泛地相互作用，许多项目之间的正式合作 具有重叠利益的领导者，并由三个核心（组织成像和形态测量; 分子生物学;管理）。我们的共同目标是更好地了解Oatransport如何在 环境和几个关键器官的线粒体作为衰老和疾病的功能被调节， 反过来，缺氧本身如何调节其自身的可用性，从而影响这些相同的器官功能， 条件