Physiological Consequences of Hypoxia and Lung Disease

肺部疾病最重要的后果是低氧血症，导致人体的氧气供应受损。 组织，器官功能减退。本研究计划继续致力于了解 低氧血症在健康和疾病中的原因和影响。五个项目中有三个在 骨骼肌。第四项研究涉及低氧的心脏后果，第五项研究涉及神经可塑性。 缺氧。提议与本周期(26-30年)相同的五个项目负责人，贷款连续性 一个富有成效的项目。然而，实验方法已经演变为更多地关注基本面 低氧反应的机制。然而，也有研究建议将它们与人类联系起来，作为一种 年龄和疾病的作用，使得一个综合的方法来解决缺氧问题。项目1(瓦格纳) 重点阐述了健康和健康人肌肉血管生成对低氧反应的基本分子机制 疾病；项目2(Mathieu-Costello)使用现代形态测量方法评估局部心肌梗死 可获得性以及慢性缺氧和衰老对此的影响；项目3(Richardson)检查了这些影响 从宏观角度综合研究衰老对人体肌肉结构和功能的影响 成像到分子生物学；项目4(鲍威尔)解决了低氧对神经功能的影响 参与呼吸控制，整合分子和生理工具；项目5(Hogan)调查 OaAvailable对单个肌纤维功能的影响 和分子方法。这些项目相互作用广泛，许多项目正式成为项目之间的共同努力 具有重叠兴趣的领导者，并由三个核心支持(组织成像和形态计量学； 分子生物学；管理学)。我们的共同目标是更好地了解奥特拉如何在 环境和几个关键器官的线粒体是作为衰老和疾病的功能进行调节的， 反过来，低氧本身是如何调节自身的可用性，从而影响这些器官的功能的 条件。^

The most important consequence of lung disease is hypoxemia resulting in impaired oxygen supply to the tissues, 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. ^