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.

颗粒物质空气污染<2.5µm（PM2.5）是全球领先的环境风险因素， 与艾滋病，疟疾，结核病和战争/饥荒相结合的贡献更多。 与PM2.5相关的健康风险主要来自心血管（CV）的原因，以及数据 由于诸如2型糖尿病之类的疾病，支持了重大的公共卫生影响。建立在 我们的研究计划取得了巨大的成功，这在很大程度上提供了基础 我们了解PM2.5诱导的心脏代谢性疾病的机制的基础，我们提出 转化投资的创新框架。我们的新数据提供了引人注目的链接 在PM2.5暴露和昼夜节律（CR）通过表观遗传重编程造成的破坏之间 导致代谢功能障碍和胰岛素抵抗。按照Niehs翻译 研究框架，我们提出了一个雄心勃勃的计划，其中包含8年的3个目标，这将 包含涉及集中环境PM2.5暴露（动物）和人类的统一研究 跨环境暴露范围的干预试验，由 基因组广泛的关联和孟德尔随机化方法，将确定空气的途径 污染介导的简历风险。利用正在进行的平移空气污染的临床试验 在北京的脆弱人群中使用个性化策略，并通过一项新研究 涉及缓解空气污染（我的空气），我们将评估降低暴露的影响 在CR中断/睡眠和代谢端点上。总的来说，该项目的结果将有助于棚屋 关于空气污染的重要新灯，其对CR和心脏代谢性疾病的影响并提供 关于个人干预策略受保护影响的有影响力数据，这些策略可能会改变 公共卫生政策。