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：
10349277
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/10349277
关键词：
ATAC-seq Acute Disease Air Pollutants Air Pollution Animals Anti-Inflammatory Agents Antioxidants Arterial Fatty Streak Arteries Atherosclerosis Bone Marrow Transplantation Cardiometabolic Disease Cardiovascular Diseases Cells 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 Genes Health Human Immune Impairment In Vitro Inflammation Inflammatory Ingestion Inhalation Injections Intervention Laboratories Lesion Link Lip structure Lipids 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 Pathway interactions Pharmacology Phenotype Plasma Play Population Predisposition Public Health Regimen Resolution Risk Risk Factors Role Sampling Series Serum Sorting - Cell Movement Stress Testing Therapeutic Intervention Time Up-Regulation Work air filter attributable mortality base cardiometabolic risk cardiovascular effects cardiovascular risk factor cytokine dietary dietary manipulation epigenomics fine particles in vivo irradiation macrophage metabolomics monocyte mortality novel nuclear factor-erythroid 2 oxidation peripheral blood 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.

项目摘要 PM2.5是发病率和死亡率的全球领先危险因素，是领先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在诸如2型糖尿病之类的慢性疾病中发挥作用心血管疾病一直是我们和我们和其他的。在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与途径在心脏代谢疾病中起病因的作用。我们的发现和评论从根本上有塑造了对PM2.5及其与心脏代谢风险增加的影响的理解疾病。特别是，我们的小组通过 ROS和炎症依赖性途径。尽管我们对助长道路的理解有助于疾病的进展已大大增强，涉及解决的机制炎症和对分辨率途径失调的理解有助于疾病进展受到限制。确定这些机制可能为新机会铺平道路靶向非空气污染介导的心血管风险，但其他普遍的健康风险。通过实施三个特定目的的该提案试图：1）表征空气污染引起的变化炎症分辨率途径； 2）确定这些途径在多大程度上与饮食重叠操纵； 3）确定潜在的干预策略以促进保守分辨率的上调响应空气污染引起的炎症的途径。