DISCOVER Center: Cardiovascular Disease and Traffic-Related Air Pollution

描述(由申请人提供) 这个发现中心的总体目标是通过整合一套不同的研究方法，调查与交通相关的空气污染导致心肌梗死和其他心血管疾病的机制。空气污染暴露一直与心血管疾病有关。越来越多的文献表明，空气污染对心血管健康影响的主要来源是暴露在交通中。柴油尾气是一种极好的曝光模式。该发现中心的一系列密切相关的活动将试图了解与暴露相关的影响的潜在机制(导致血管收缩和动脉粥样硬化加速的分子机制)，并利用环境暴露来了解有关血管生物学的基本机制。这些研究将通过先进的暴露评估方法利用实验和流行病学研究中的暴露对比，以及人类和动物研究中的遗传多样性，以促进我们的目标。该应用程序汇集了一个由五个项目(两个以患者为中心和三个基础机械学研究)和三个核心--行政、暴露科学、生物统计和生物信息学--组成的具有凝聚力的小组。项目1调查受控暴露于柴油废气后人体血管反应的机制；项目2在一项基于人群的观察性研究中研究与交通相关的空气污染对血管反应和动脉粥样硬化的影响的遗传修饰物。项目3调查了全身炎症在柴油机尾气的血管反应中的作用。项目4研究柴油机尾气暴露对心肌损伤和细胞凋亡的影响。项目5调查了柴油机尾气对血管的反应中的活性氧物种和氧化应激。通过这项研究，研究人员将获得可用于制定预防和治疗策略的知识。 计划的综合性(临床和基础)和跨学科性质

DESCRIPTION (provided by applicant) The overall objective of this DISCOVER Center is to investigate the mechanisms by which traffic-related air pollution causes myocardial infarction and other cardiovascular diseases, by integrating a diverse set of research approaches. Air pollution exposures have been consistently associated with cardiovascular disease. A growing literature indicates that the major source of variation in air pollution's cardiovascular health effects is from exposure to traffic. Diesel exhaust is an excellent model exposure. The closely linked suite of activities in this DISCOVER Center will attempt to understand the mechanisms (molecular mechanisms that cause vasoconstriction and acceleration of atherosclerosis) underlying exposure-related effects, and use environmental exposures to understand basic mechanisms regarding vascular biology. The studies will exploit exposure contrasts in experimental and epidemiological studies through advanced exposure assessment methods, and genetic diversity in both human and animal studies, to advance our aims. The application brings together a cohesive group of five projects (two patient-oriented and three basic mechanistic studies) and three cores, Administrative, Exposure Science, and Biostatistics and Bioinformatics. Project 1 investigates the mechanism underlying vascular response in humans following controlled exposure to diesel exhaust; Project 2 studies genetic modifiers on the effect of traffic-related air pollution on vascular response and atherosclerosis in a population-based human observational study. Project 3 investigates the role of systemic inflammation in the vascular response to diesel exhaust. Project 4 investigates the impact of diesel exhaust exposure on myocardial injury and apoptosis. Project 5 investigates reactive oxygen species and oxidative stress in the vascular response to diesel exhaust. Through this research, the investigators will develop knowledge that can be used to develop preventive and therapeutic strategies. INTEGRATED (clinical and basic) and INTERDISCIPLINARY NATURE OF PROGRAM