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

多样性补充剂（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: 10675939
• 负责人: Sanjay Rajagopalan
• 金额: $ 6.26万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-10 至 2029-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10675939
• 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; cohort; genome wide association study; innovation; mortality; personalized intervention; personalized strategies; prevent; programs; protective effect; success; translational clinical trial; translational framework

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.

颗粒物空气污染2.5微米(PM2.5)是全球主要的环境风险因素， 对全球死亡率的贡献超过了艾滋病、疟疾、结核病和战争/饥荒的总和。 数据显示，与PM2.5相关的健康风险主要来自心血管原因 支持因2型糖尿病等疾病造成的重大公共卫生影响。建立在 我们的研究项目取得了重大成功，这在很大程度上为我们提供了 为我们理解PM2.5引起的心脏代谢紊乱的机制，我们提出 翻译调查的创新框架。我们的新数据提供了令人信服的链接 在PM2.5暴露和通过表观遗传重新编程扰乱昼夜节律(CR)之间， 导致代谢功能障碍和胰岛素抵抗。根据NIEHS翻译 研究框架，我们提出了一个雄心勃勃的计划，包括在8年内实现3个目标，将 包含涉及环境PM2.5集中暴露(动物)和人类的协调研究 环境暴露范围内的干预试验，由以下结果预测和支持 全基因组关联和孟德尔随机化方法，将识别空气的路径 污染中介了心血管风险。利用正在进行的减少空气污染的转化性临床试验 在北京弱势群体中使用个性化策略，并通过一项新的研究 在缓解空气污染方面，我们将评估减少接触的影响。 CR干扰/睡眠和新陈代谢终点。总体而言，这个项目的成果将有助于 关于空气污染及其对CR和心脏代谢性疾病的影响并提供 个人干预策略的保护效果的有影响力的数据，这些加在一起可能会改变 公共卫生政策。