Targets and targeting of immunometabolism in chronic PM2.5 exposure

慢性 PM2.5 暴露中免疫代谢的目标和靶向

基本信息

批准号：
10563199
负责人：
Andrei Maiseyeu
金额：
$ 40.25万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-07 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10563199
关键词：
ATAC-seq Acceleration Acute Disease Air Pollutants Air Pollution Animals Anti-Inflammatory Agents Antioxidants Arterial Fatty Streak Arteries Atherosclerosis Bone Marrow Transplantation Cardiometabolic Disease Cardiovascular Diseases Cells ChIP-seq Cholesterol Chronic Chronic Disease Data Diet Dietary Intervention Disease Progression Donor person Environment Environmental Risk Factor Enzymes Erythroid Etiology Exposure to Fatty acid glycerol esters Fingerprint Flow Cytometry Fluorescence GATA1 gene Genes Health Human Immune Impairment In Vitro Inflammation Inflammatory Ingestion Inhalation Injections Intervention Laboratories Lesion Link Lip structure Lipids Macrophage Maps Mass Spectrum Analysis Mediating Meta-Analysis Metabolic Metabolic Diseases Modeling Molecular Morbidity - disease rate Mus Myelogenous Myeloid Cells Non-Insulin-Dependent Diabetes Mellitus Nuclear PTPRC gene Particulate Particulate Matter Pathway interactions Phenotype Plasma Play Population Predisposition Public Health Regimen Resolution Risk Risk Factors Role Sampling Series Serum Shapes Sorting Stress Testing Therapeutic Intervention Time Up-Regulation Work air filter attributable mortality cardiometabolic risk cardiovascular effects cardiovascular risk factor cytokine dietary dietary manipulation epigenomics fine particles in vivo irradiation metabolomics meter monocyte mortality novel nuclear factor-erythroid 2 oxidation peripheral blood pharmacologic response systematic review transcriptome sequencing transcriptomics

项目摘要

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.

项目概要 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关。最近的数据表明，PM2.5 和/或与交通相关的空气污染物可能会在 2 型糖尿病等慢性疾病中发挥作用，进而可能导致对以下疾病的易感性心血管疾病，已成为我们和美国多个系统评价和荟萃分析的主题其他的。在对动物和人类进行的一系列研究中，我们提供了令人信服的证据，证明 PM2.5 与在心脏代谢疾病中发挥病因作用的途径。我们的调查结果和评论从根本上形成了对 PM2.5 影响及其与心脏代谢风险增加之间关系的理解疾病。特别是，我们的小组通过以下方法证明了长期暴露于 PM2.5 的促动脉粥样硬化作用： ROS 和炎症依赖性途径。尽管我们对途径的理解有助于疾病的进展已显着增强，解决问题的机制炎症以及对消退途径失调如何导致疾病的理解进展受到限制。确定这些机制可以为新的机会铺平道路不仅针对空气污染介导的心血管风险，还针对其他普遍的健康风险。通过该提案旨在实现三个具体目标：1）描述空气污染引起的变化的特征炎症消退途径； 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应对空气污染引起的炎症的途径。