(CIRCADIAN) Circadian Disruption as Mediator of Cardiometabolic Risk in Air Pollution

（昼夜节律）昼夜节律紊乱是空气污染中心脏代谢风险的调节因素

• 批准号: 10653695
• 负责人: Sanjay Rajagopalan
• 金额: $ 96.04万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-17 至 2029-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10653695
• 关键词: Acquired Immunodeficiency Syndrome; Air; Air Pollution; Animals; Biological; Cardiometabolic Disease; Cardiovascular system; Circadian Dysregulation; Circadian Rhythms; Data; Disease; Environmental Risk Factor; Epigenetic Process; Famines; Goals; Health; Health Policy; Heart; Human; Influentials; Insulin Resistance; Intervention; Intervention Trial; Light; Link; Malaria; Mediating; Mediator; Mendelian randomization; Metabolic; Metabolic dysfunction; Morbidity - disease rate; National Institute of Environmental Health Sciences; Non-Insulin-Dependent Diabetes Mellitus; Particulate Matter; Pathway interactions; Public Health; Research; Risk; Sleep; Translational Research; Tuberculosis; Vulnerable Populations; War; cardiometabolic risk; cardiovascular risk factor; circadian; cohort; genome wide association study; innovation; mortality; personalized intervention; personalized strategies; prevent; programs; protective effect; success; translational clinical trial; translational framework

ABSTRACT Particulate matter air pollution <2.5µm (PM2.5) is the leading environmental risk factor globally, contributing more to global mortality than AIDS, malaria, tuberculosis and wars/famines combined. The health risks associated with PM2.5 are predominantly from cardiovascular (CV) causes, with data supporting a major public health impact due to disorders such as type 2 diabetes. Building on the substantial successes of our research program, that in large part have provided the foundational basis for our understanding of mechanisms of PM2.5-induced cardiometabolic disorders, we propose an innovative framework of translational investigations. Our new data provide compelling links between PM2.5 exposure and circadian rhythm (CR) disruption through epigenetic reprogramming, resulting in metabolic dysfunction and insulin resistance. In accordance with the NIEHS Translational Research Framework, we propose an ambitious plan encompassing 3 goals over 8 years that will encompass harmonized studies involving concentrated ambient PM2.5 exposures (animal) and human intervention trials across the ambient exposure spectrum, predicated and supported by results from genome wide association and mendelian randomization approaches, that will identify pathways of air pollution mediated CV risk. Leveraging on-going translational clinical trials of air pollution reduction using personalized strategies in vulnerable populations in Beijing, and through one new study involving mitigation of air pollution (ITS-MY-AIR), we will evaluate the impact of exposure reduction on CR disruption/sleep and metabolic endpoints. Collectively, results from this project will help shed important new light on air pollution, its impact on CR and cardiometabolic disorders and provide influential data on protective effects of personal intervention strategies, that together could change public health policy.

摘要