(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: 10862217
• 负责人: Sanjay Rajagopalan
• 金额: $ 12.03万
• 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/10862217
• 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.

抽象的 颗粒物质空气污染<2.5µm（PM2.5）是全球领先的环境风险因素，贡献更多 全球死亡率比艾滋病，疟疾，结核病和战争/饥荒加在一起。健康风险与 PM2.5主要来自心血管（CV）的原因，数据支持重大的公共卫生影响 由于诸如2型糖尿病之类的疾病。以我们的研究计划取得的巨大成功为基础 很大一部分为我们理解PM2.5诱导的机制提供了基础基础 心脏代谢疾病，我们提出了转化研究的创新框架。我们的新数据 通过表观遗传学的PM2.5暴露与昼夜节律（CR）破坏之间提供引人注目的联系 重编程，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，其中包括8年内3个目标 包含涉及集中环境PM2.5暴露（动物）和人类的统一研究 基因组的结果预测和支持的整个环境暴露范围的干预试验 广泛的关联和孟德尔随机化方法，这些方法将确定介导的空气污染途径 简历风险。使用个性化策略利用正在进行的临床试验减少空气污染的临床试验 北京的脆弱人群，以及一项涉及缓解空气污染（我的空气）的新研究， 我们将评估降低暴露对CR干扰/睡眠和代谢终点的影响。共同 该项目的结果将有助于为空气污染，其对CR和心脏代谢的影响留下重要的新启示。 疾病并提供有关个人干预策略保护性影响的有影响力的数据，可以一起 改变公共卫生政策。

项目成果

N95 Respirators for Cardiovascular Protection During Wildfire Smoke Events.

用于野火烟雾事件期间心血管保护的 N95 呼吸器。

• DOI: 10.1161/jaha.123.032422
• 发表时间: 2024
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4
• 作者: Brook,RobertD;Rajagopalan,Sanjay;Al-Kindi,Sadeer
• 通讯作者: Al-Kindi,Sadeer

Geographically Weighted Modeling to Explore Social and Environmental Factors Affecting County-Level Cardiovascular Mortality in People With Diabetes in the United States: A Cross-Sectional Analysis.

地理加权模型探索影响美国县级糖尿病患者心血管死亡率的社会和环境因素：横断面分析。

• DOI: 10.1016/j.amjcard.2023.09.084
• 发表时间: 2023
• 期刊: The American journal of cardiology
• 作者: Zelko,Andrea;Salerno,PedroRVO;Al-Kindi,Sadeer;Ho,Fredrick;Rocha,FannyPetermann;Nasir,Khurram;Rajagopalan,Sanjay;Deo,Salil;Sattar,Naveed
• 通讯作者: Sattar,Naveed

Residual environmental risk in patients with cardiovascular disease: an overlooked paradigm.

心血管疾病患者的残留环境风险：一个被忽视的范例。

• DOI: 10.1093/eurheartj/ehad412
• 发表时间: 2023
• 期刊: European heart journal
• 影响因子: 39.3
• 作者: Al-Kindi,Sadeer;Paneni,Francesco;Brook,RobertD;Rajagopalan,Sanjay
• 通讯作者: Rajagopalan,Sanjay

Excess Global Blood Pressure Associated With Fine Particulate Matter Air Pollution Levels Exceeding World Health Organization Guidelines.

• DOI: 10.1161/jaha.122.029206
• 发表时间: 2023-04-18
• 期刊: JOURNAL OF THE AMERICAN HEART ASSOCIATION
• 影响因子: 5.4
• 作者: Brook, Robert D.;Motairek, Issam;Rajagopalan, Sanjay;Al-Kindi, Sadeer
• 通讯作者: Al-Kindi, Sadeer

Microplastics and Nanoplastics in Atheromas and Cardiovascular Events.

• DOI: 10.1056/nejmoa2309822
• 发表时间: 2024-03
• 期刊: The New England journal of medicine
• 作者: Raffaele Marfella;F. Prattichizzo;C. Sardu;Gianluca Fulgenzi;Laura Graciotti;Tatiana Spadoni;N. D’Onofrio;L. Scisciola;Rosalba La Grotta;Chiara Frigé;Valeria Pellegrini;Maurizio Municinò;M. Siniscalchi;Fabio Spinetti;Gennaro Vigliotti;C. Vecchione;A. Carrizzo;G. Accarino;Antonio Squillante;G. Spaziano;D. Mirra;Renata Esposito;Simona Altieri;Giovanni Falco;A. Fenti;Simona Galoppo;S. Canzano;F. C. Sasso;Giulia Matacchione;Fabiola Olivieri;F. Ferraraccio;I. Panarese;P. Paolisso;Emanuele Barbato;Carmine Lubritto;M. Balestrieri;C. Mauro;Augusto E Caballero;Sanjay Rajagopalan;Antonio Ceriello;Bruno D'Agostino;P. Iovino;Giuseppe Paolisso