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

• 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
• 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

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/或与交通有关的空气污染物可能 在2型糖尿病等慢性疾病中发挥作用，这反过来又可能使人对糖尿病易感。 心血管疾病，并已成为我们进行的多项系统综述和荟萃分析的主题， 他人在一系列对动物和人类的研究中，我们提供了令人信服的证据，将PM2.5与 在心脏代谢疾病中发挥病因作用的途径。我们的调查结果和审查从根本上 塑造了对PM2.5的影响及其与心脏代谢风险增加的关系的理解 疾病特别是，我们的研究小组已经证明了慢性PM2.5暴露的促动脉粥样硬化作用， ROS和炎症依赖性通路。尽管我们对导致 疾病的进展已经大大加快，参与解决的机制， 炎症和了解如何失调的决议途径有助于疾病 进展有限。查明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，而且针对其他普遍的健康风险。通过 实施三个具体目标这项建议旨在：1）描述空气污染引起的变化， 炎症解决途径; 2）确定这些途径与饮食的重叠程度 3）确定潜在的干预策略，以促进保守的分辨率上调 对空气污染引起的炎症作出反应的途径。