Targets and targeting of immunometabolism in chronic PM2.5 exposure

项目摘要 PM2.5是全球发病率和死亡率的主要风险因素，也是主要的环境因素 与心血管疾病有牵连。最近的数据表明，PM2.5和/或与交通相关的空气污染物可能 在慢性疾病中发挥作用，如2型糖尿病，这可能反过来增加易感性 心血管疾病，并已成为我们和 其他。在对动物和人类的一系列研究中，我们提供了令人信服的证据，将PM2.5与 在心脏代谢性疾病中起病因学作用的途径。我们的发现和审查从根本上说 形成了对PM2.5的影响及其与心脏代谢风险增加的关联的理解 疾病。特别是，我们的团队通过以下方式展示了慢性PM2.5暴露的促动脉粥样硬化作用 ROS和炎症依赖通路。尽管我们对路径的理解有助于 疾病的进展已显著增强，参与解决 炎症和对分解途径的失调如何导致疾病的理解 进展有限。确定这些机制可以为新的机会铺平道路 目标不仅是空气污染导致的心血管风险，还包括其他普遍存在的健康风险。通过 实施本提案寻求的三个具体目标：1)描述空气污染引起的变化 炎症消解途径；2)确定这些途径与饮食重叠的程度 操纵；3)确定潜在的干预策略以促进保守分辨率的上调 空气污染引起炎症的反应途径。

Project Summary PM2.5 is a leading global risk factor for morbidity and mortality and is the leading environmental factor implicated in cardiovascular disease. Recent data suggest that PM2.5 and/or traffic-related air pollutants may play a role in chronic diseases such as Type 2 diabetes mellitus, that may in turn confer susceptibility to cardiovascular disease and has been the topic of multiple systematic reviews and meta-analysis by us and others. In a series of studies in animals and humans, we have provided convincing evidence linking PM2.5 to pathways playing an etiologic role in cardiometabolic disease. Our findings and reviews have fundamentally shaped the understanding of the effects of PM2.5 and its association with increased risk of cardiometabolic disease. In particular, our group has demonstrated pro-atherogenic effects of chronic PM2.5 exposure, through ROS and inflammation dependent pathways. Although our understanding of pathways contributing to progression of disease has been dramatically enhanced, the mechanisms involved in the resolution of inflammation and an understanding of how dysregulation of resolution pathways contributes to disease progression has been limited. Identification of these mechanisms could pave the way for new opportunities to target non only air pollution mediated cardiovascular risk but other pervasive health risks. Through the implementation of three specific aims this proposal seeks to: 1) characterize air pollution-induced changes in inflammation resolution pathways; 2) determine to what extent these pathways overlap with dietary manipulation; 3) identify potential intervention strategies to promote upregulation of conserved resolution pathways in response to air pollution-induced inflammation.