Oxidative Stress in Sleep Apnea and Cardiac Disease

睡眠呼吸暂停和心脏病中的氧化应激

• 批准号: 7281640
• 负责人: Reena Mehra
• 金额: $ 13.47万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7281640
• 关键词: Oxidative; Stress; Sleep; Apnea; Cardiac

DESCRIPTION (provided by applicant): I am an Assistant Professor of Medicine in the Divisions of Pulmonary/Critical Care/Sleep Medicine and Epidemiology/Biostatistics, and a recent graduate of Clinical Research Scholars Program, which awards a Master of Science in Clinical Research degree. My goals are to develop independent research aimed to answer fundamental questions regarding cardiovascular disease (CVD) outcomes of sleep disordered breathing (SDB). I am interested in blending epidemiological and translational approaches to identify individuals at highest risk for developing SDB-related CVD, and to clarify underlying disease mechanisms. This award will further expand research skills, providing an intense hands-on training experience aimed at: 1.) Honing skills in conducting rigorous randomized controlled studies and analyzing large epidemiological datasets, 2.) Gaining new skills in relevant translational research related to utilizing state-of-the-art bioassays, and 3.) Understanding how to optimally incorporate non-invasive cardiac function tests in epidemiological studies; with immediate applications to the proposed research. The objective of this proposal is the rigorous systematic assessment of the role of oxidative stress as a primary culprit in the pathophysiologic pathway linking SDB and CVD. First, a cross sectional analysis will be performed using existing blood and urine specimens collected on a large cohort, assessing between individual differences in oxidative stress markers from carefully chosen general and specific pathways to assess relationships between indices of SDB and oxidative stress. This will also allow me to hone writing/ analytic skills and inform future analyses. Secondly, I have designed an independent randomized, controlled, parallel design trial assessing the impact of SDB treatment (i.e. reversal of hypoxemia, etc.) on levels of oxidative stress markers. Also, secondary treatment effects on endothelial dysfunction (evaluated by brachial ultrasound), inflammation, insulin resistance and blood pressure will be assessed, including an evaluation of how observed treatment effects may be mediated by levels of oxidative stress. A logistically feasible five-year training program is proposed with a team of faculty mentors from strong research departments. This proposal addresses important knowledge gaps regarding the physiologic basis of the SDB-CVD relationship. Clarification of the role of oxidative stress will allow for use as potential stratification and prediction of CVD outcomes in individuals with SDB. The proposal will provide a key training opportunity to foster my development as an independent clinical epidemiologist with commitment to patient-based research in sleep medicine and cardiopulmonary disease.

描述（由申请人提供）： 我是肺/重症监护/睡眠医学部门的医学助理教授， 流行病学/生物统计学，和临床研究学者计划，该计划授予临床研究硕士学位的应届毕业生。我的目标是开展独立的研究，旨在回答有关睡眠呼吸障碍（SDB）的心血管疾病（CVD）结果的基本问题。我有兴趣将流行病学和转化方法结合起来，以识别患有SDB相关心血管疾病的最高风险个体，并阐明潜在的疾病机制。该奖项将进一步扩大研究技能，提供密集的实践培训经验，旨在：1。磨练进行严格的随机对照研究和分析大型流行病学数据集的技能，2。获得与利用最先进的生物测定相关的相关转化研究的新技能，以及3。了解如何最佳地将非侵入性心脏功能测试纳入流行病学研究;并立即应用于拟议的研究。该提案的目的是严格系统地评估氧化应激作为连接SDB和CVD的病理生理途径中的罪魁祸首的作用。首先，将使用在大型队列中收集的现有血液和尿液样本进行横断面分析，评估来自精心选择的一般和特定途径的氧化应激标志物的个体差异，以评估SDB指数与氧化应激之间的关系。这也将使我磨练写作/分析技能，并为未来的分析提供信息。其次，我设计了一项独立的随机、对照、平行设计试验，评估SDB治疗的影响（即低氧血症的逆转等）。氧化应激指标的水平。此外，还将评估对内皮功能障碍（通过肱动脉超声评价）、炎症、胰岛素抵抗和血压的次要治疗效果，包括评价观察到的治疗效果如何通过氧化应激水平介导。一个后勤可行的五年培训计划，提出了一个团队的教师导师从强大的研究部门。该提案解决了关于SDB-CVD关系的生理基础的重要知识缺口。阐明氧化应激的作用将允许用作SDB个体中CVD结局的潜在分层和预测。该提案将提供一个关键的培训机会，以促进我作为一名独立的临床流行病学家的发展，致力于以患者为基础的睡眠医学和心肺疾病研究。