Air Pollution, Circadian Rhythm Disruption and Cardiometabolic Disease

空气污染、昼夜节律紊乱和心脏代谢疾病

• 批准号: 9906926
• 负责人: Petra Haberzettl
• 金额: $ 34.46万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9906926
• 关键词: ARNTL gene; Aerosols; Affect; Air; Air Pollution; Animal Model; Aorta; Attenuated; Biochemical Process; Biological; Biological Availability; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Characteristics; Circadian Dysregulation; Circadian Rhythms; Data; Deposition; Development; Diabetes Mellitus; Diet; Disease; Eating; Endothelium; Exposure to; Gene Expression; Genes; Goals; Health; Human; Individual; Industrialization; Injury; Insulin Resistance; Knockout Mice; Laboratories; Lead; Life Style; Light; Link; Lung; Mediating; Metabolism; Modeling; Modernization; Mus; Nitric Oxide Synthase; Non-Insulin-Dependent Diabetes Mellitus; Oxidation-Reduction; Oxidative Stress; Particulate; Periodicity; Peripheral; Phase; Physiological Processes; Policies; Pollution; Post-Translational Protein Processing; Predisposition; Prevention strategy; Research; Sleep Deprivation; System; Testing; Toxic effect; Transcriptional Regulation; Urbanization; Work; air filter; ambient air pollution; atherogenesis; base; cardiometabolic risk; cardiometabolism; cardiovascular disorder risk; chemical property; circadian; diabetes risk; epidemiologic data; evidence based guidelines; mortality; mouse model; novel; overexpression; particle; physical property; pollutant; premature; prevent; response; sleep behavior; vascular injury

Abstract Exposure to ambient air pollution has been linked to annually 7 million premature deaths worldwide and 200,000 in the US and the global burden of air pollution is likely to increase due to increasing urbanization and industrialization. Extensive research has shown that exposure to particulate air pollution and specifically fine particulates (PM2.5) increase the risk of cardiovascular disease and diabetes. However, despite this extensive evidence, it is unclear how PM2.5 exposure increases the cardiometabolic risk and which susceptible states increase the sensitivity to vascular and cardiometabolic injury due to PM2.5 exposure. In our proposed studies we attempt to disentangle the mechanism leading to the toxicity of PM2.5 by testing the novel hypothesis that PM2.5 disrupts vascular circadian rhythms and that this contributes to the development of cardiometabolic disease in a new susceptibility state of circadian dyssynchrony. This hypothesis is supported by our preliminary data showing that that exposure to concentrated ambient PM2.5 (CAP) alters the rhythmic expression of clock genes in the murine aorta and increases insulin resistance in mice with the disturbed light/dark cycle (circadian dyssynchrony). As this models a real-world scenario in which individuals with disturbed light cycle (e.g. due to light pollution, sleep deprivation) are exposed to air pollution it is of high relevance to our modern urban 24 h lifestyle associated with air and light pollution and changes in sleep behavior. Successful completion of this project will identify new targets of and novel susceptibility states (circadian dyssynchrony and chronotoxicity) for PM2.5 toxicity. Results of theses studies will be of significance in understanding the adverse health effects originated from our modern lifestyle and could ultimately lead to the development of evidence-based guidelines and policies to minimize the cardiometabolic effects of urbanization and pollutant exposure.

抽象的 暴露于环境空气污染与每年700万人过早死亡有关 全球和200,000在美国，全球空气污染负担可能会增加 增加城市化和工业化。广泛的研究表明，接触 颗粒空气污染，特别是细微粒（PM2.5）增加了 心血管疾病和糖尿病。但是，尽管有很多证据，但尚不清楚 PM2.5暴露如何增加心脏代谢风险和哪些易感状态增加 PM2.5暴露引起的血管和心脏代谢损伤的敏感性。在我们的建议中 研究我们试图通过测试来解散导致PM2.5毒性的机制 新的假设PM2.5破坏了血管昼夜节律，这有助于 在新的易感性状态下，心脏代谢疾病的发展。 我们的初步数据证明了这一假设的支持 环境PM2.5（CAP）改变了鼠主动脉中时钟基因的节奏表达和 通过受干扰的光/黑暗周期（昼夜节律异议障碍）增加小鼠的胰岛素耐药性。 因为这模拟了一个现实世界中的情况，在该场景中，光周期干扰的人（例如 光污染，睡眠剥夺）暴露于空气污染，这与我们的 现代城市24 H生活方式与空气和光污染以及睡眠变化有关 行为。该项目的成功完成将确定新的目标和新颖的目标 PM2.5毒性的易感性状态（昼夜节律症状和表年毒性）。结果 这些研究将在理解不良健康效应起起源于 我们的现代生活方式，最终可能导致制定基于证据的准则 以及最小化城市化和污染物暴露的心脏代谢作用的政策。