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Oxidative Stress in Sleep Apnea and Cardiac Disease

睡眠呼吸暂停和心脏病中的氧化应激

基本信息

批准号：
7923320
负责人：
Reena Mehra
金额：
$ 10.66万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
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/7923320
关键词：
Address African American Amino Acids Apnea Arginine Arousal Arts Award Biochemical Markers Biological Assay Biological Markers Biometry Blood Blood Pressure Blood specimen Cardiology Cardiovascular Diseases Cell Respiration Ceruloplasmin Chronic Clinical Clinical Research Clinical Trials Design Comorbidity Continuous Positive Airway Pressure Coupled Critical Care Cross-Sectional Studies Data Collection Data Set Databases Development Diagnostic Disease Disease Outcome Enrollment Ensure Epidemiologic Studies Epidemiologist Epidemiology Evaluation F2-Isoprostanes Faculty Family Study Fostering Foundations Functional disorder Future Genetic Polymorphism Goals Hand Heart Diseases Heart Function Tests Hypoxemia Hypoxia Individual Individual Differences Inflammation Insulin Resistance Interleukin-6 Investigation Knowledge Link Lung Manuscripts Master of Science Measures Mediating Medicine Mentors Morbidity - disease rate NCI Scholars Program Nitric Oxide Nitric Oxide Pathway Outcome Outcome Measure Oxidants Oxidative Stress Oxidative Stress Pathway Oxygen Participant Pathogenesis Pathway interactions Patients Peroxidases Pharmacotherapy Physiological Placebos Plasma Positioning Attribute Productivity Publications Pulmonary Heart Disease Pulmonology Randomized Randomized Controlled Trials Reactive Oxygen Species Recruitment Activity Research Research Design Research Personnel Research Training Risk Role Secure Severities Sleep Sleep Apnea Syndromes Sleep Fragmentations Specimen Stratification Training Training Programs Translational Research Ultrasonography Urine Work Writing base brachial artery cardiovascular disorder risk career career development cohort design expectation experience high risk improved indexing inflammatory marker innovation insight interest molecular marker professor skills translational approach treatment effect

项目摘要

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)：我是肺科/重症监护科/睡眠医学部的助理教授流行病学/生物统计学，以及最近毕业的临床研究学者方案，该方案授予临床研究理学硕士学位。我的目标是开展独立的研究，旨在回答有关睡眠呼吸紊乱(SDB)的心血管疾病(CVD)后果的基本问题。我感兴趣的是将流行病学和翻译方法结合起来，以确定与SDB相关的心血管疾病的最高风险个体，并阐明潜在的疾病机制。该奖项将进一步扩展研究技能，提供针对以下目标的高强度动手培训体验：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.获得与使用最先进的生物检测方法有关的相关翻译研究的新技能，以及3.)了解如何在流行病学研究中以最佳方式合并非侵入性心功能测试；并立即应用于拟议的研究。这项建议的目的是严格系统地评估氧化应激作为联系SDB和CVD的病理生理途径中的主要罪魁祸首的作用。首先，将使用在大队列中收集的现有血液和尿液样本进行横断面分析，从精心选择的一般和特定途径评估氧化应激标志物的个体差异，以评估SDB指标和氧化应激之间的关系。这也将让我磨练写作/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(即逆转低氧血症等)的影响。氧化应激标志物的水平。此外，还将评估对内皮功能障碍(通过臂部超声评估)、炎症、胰岛素抵抗和血压的二级治疗效果，包括评估观察到的治疗效果可能如何通过氧化应激水平进行调节。一项后勤上可行的五年培训计划被提出，由来自强大研究部门的教师导师组成的团队。这项建议解决了有关SDB-CVD关系的生理学基础的重要知识空白。明确氧化应激的作用将允许将其用作SDB患者心血管疾病结局的潜在分层和预测。这项提案将提供一个关键的培训机会，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。