DISCOVER Center: Cardiovascular Disease and Traffic-Related Air Pollution

探索中心的总体目标是通过整合多种研究方法，研究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。接触空气污染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。柴油废气是一个极好的模型曝光。该探索中心的一系列紧密相关的活动将试图了解暴露相关的机制（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血管生物学的基本机制。这些研究将利用实验和流行病学研究中的暴露对比，通过先进的暴露评估方法，以及人类和动物研究中的遗传多样性，来推进我们的目标。该申请汇集了五个项目（两个面向患者和三个基础机制研究）和三个核心，行政管理，暴露科学，生物统计学和生物信息学。

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.