Mechanisms for Cardiovascular Effects of air pollutants: Effect of Age and Sex

空气污染物对心血管影响的机制：年龄和性别的影响

• 批准号: 7941803
• 负责人: NAOMI K FUKAGAWA
• 金额: $ 49.7万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-28 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7941803
• 关键词: Affect; Age; Agriculture; Air Pollutants; Air Pollution; Airborne Particulate Matter; Alveolar Macrophages; Animal Disease Models; Animals; Apolipoprotein E; Asbestos; Atherosclerosis; Attenuated; Autoimmune Diseases; Belief; Biological; Breathing; CD4 Positive T Lymphocytes; Carbon Monoxide; Cardiovascular Diseases; Cardiovascular system; Cell Death; Chronic; Chrysotile; Dendritic Cells; Development; Diesel Fuels; Disease; Elderly; Elderly woman; Energy-Generating Resources; Engine Exhaust; Engineering; Environment; Environmental Engineering technology; Environmental Impact; Environmental Risk Factor; Europe; Exposure to; Fatty acid glycerol esters; Fiber; Future; Gender; Grant; Growth; Health; Heart; Heart Diseases; Human; Hydrocarbons; Hypersensitivity; Immune; Inflammatory Response; Intervention; Knockout Mice; Laboratories; Lead; Lung; Lung diseases; Medicine; Mitogen-Activated Protein Kinases; Molecular Genetics; Mus; NF-kappa B; Ozone; Particulate; Particulate Matter; Pathology; Pathway interactions; Petroleum; Phase; Predisposition; Prevention; Production; Public Health; Reaction; Reporting; Research Personnel; Research Project Grants; Respiratory System; Risk Factors; Rodent Model; Scientist; Sex Characteristics; Signal Pathway; T-Lymphocyte; Technology Development Study; Testing; Therapeutic Intervention; Transportation; Vegetable Oils; Vulnerable Populations; Work; age effect; ambient particle; base; biological systems; cell type; chemokine; cytokine; exhaust; falls; in vivo; insight; lung injury; meetings; mouse model; oxidation; particle; public health relevance; respiratory; response; sex

DESCRIPTION (provided by applicant): Since the 1970's, adverse health effects have been reported at unexpectedly low levels of particulate air pollution, leading scientists and public health officials to conclude that long-term exposure to combustion-related fine particulate air pollution is a significant environmental risk factor for heart and lung diseases. Despite numerous studies examining the effects of petroleum diesel (petrodiesel) exhaust emissions on the respiratory system, the mechanisms responsible for the reported adverse human health effects and pinpointing the particulate's toxic initiating species remain elusive. Biodiesel fuel made from vegetable oil or animal fat is gaining momentum as the energy source of the future both in the U.S. and Europe. Biodiesel is typically blended into conventional diesel fuel, and emission testing has shown that biodiesel emissions appear to contain reduced levels of hydrocarbons, carbon monoxide and particulate matter (PM) but a higher soluble organic fraction in the particulate phase. Advancing age is a known risk factor for atherosclerosis, and sex differences in cardiovascular disease (CVD), autoimmune disease and airway hypersensitivity have been reported. With increased evidence that air pollutants act to exacerbate CVD, it is important to determine the mechanisms responsible for the exacerbation of atherosclerosis and the influence of age and sex on the responses to inhaled particles on underlying CVD. The hypothesis to be tested is that particulate and gaseous emissions from biodiesel compared to petrodiesel combustion will differ in the extent of lung injury and adverse systemic inflammatory responses. This will lead ultimately to different degrees of exacerbation of atherosclerosis, which will be modulated by the age and sex of the animal. This proposal will establish controlled production of engine emissions to be used in inhalation studies. The particulate and gaseous components of the exhaust as well as the heterogeneous oxidation products upon reaction with ozone will be characterized. Using animal models of disease, we will identify key signaling pathways and inflammatory responses in the lung after 3- and 9-day exposures to engine exhaust and specific gaseous and particulate size fractions, quantify and determine the types of cells (e.g. dendritic cells, alveolar macrophages, CD4+ T cells) induced after exposures to engine exhaust, and determine the effects of chronic exposure to exhaust on the development of atherosclerosis in mice with a specific focus on modulation by the age and sex of the animals. These approaches will provide insight into susceptibility of vulnerable populations (women and the elderly) and approaches for intervention and therapy. PUBLIC HEALTH RELEVANCE: Biodiesel has been touted as an important strategy for energy independence as well as sustainability in terms of agricultural production and reduced environmental impact from the transportation sector, but as with petrodiesel, combustion of biodiesel produces particulate air pollution. Adverse health effects of airborne particulate matter (PM) have been reported at unexpectedly low concentrations, leading scientists and public health officials to conclude that long-term exposure to combustion-related particulate air pollution is a significant environmental risk factor for heart and lung diseases. Despite the belief that biofuels may be better for the environment and for human health, there is very limited information about the biological effects of biodiesel emissions so this proposal will compare and contrast the biological effects of emission particles from the combustion of petro- and biodiesel and the influence of age and gender on these responses in an effort to lay the groundwork for future studies aimed at elucidating the mechanisms responsible for the significant relationship between airborne PM and lung and heart disease and at developing approaches to reduce the adverse health consequences of air pollution.

描述（由申请人提供）：自20世纪70年代以来，已报告了意外低水平的颗粒空气污染对健康的不良影响，导致科学家和公共卫生官员得出结论，长期暴露于燃烧相关的细颗粒空气污染是心脏和肺部疾病的重要环境风险因素。尽管许多研究检查了石油柴油（petrodiesel）废气排放对呼吸系统的影响，但报告的对人类健康不利影响的机制以及确定颗粒物的有毒起始物质仍然难以捉摸。在美国和欧洲，由植物油或动物脂肪制成的生物柴油作为未来的能源正在获得动力。生物柴油通常与常规柴油混合，排放测试表明，生物柴油排放物中的碳氢化合物、一氧化碳和颗粒物（PM）含量降低，但颗粒相中的可溶性有机物含量较高。年龄增长是动脉粥样硬化的一个已知危险因素，心血管疾病（CVD）、自身免疫性疾病和气道超敏反应的性别差异已被报道。随着越来越多的证据表明，空气污染物的行为加剧心血管疾病，它是重要的，以确定负责动脉粥样硬化的恶化和年龄和性别对吸入颗粒对潜在的心血管疾病的反应的影响的机制。要测试的假设是，与石油柴油燃烧相比，生物柴油的颗粒和气体排放在肺损伤和不良全身炎症反应的程度上会有所不同。这将最终导致不同程度的动脉粥样硬化恶化，这将受到动物年龄和性别的调节。该提案将建立用于吸入研究的发动机排放物的受控生产。废气中的颗粒和气体成分以及与臭氧反应后的非均相氧化产物将被表征。使用疾病的动物模型，我们将确定在暴露于发动机废气和特定气体和颗粒尺寸分数3天和9天后肺中的关键信号通路和炎症反应，量化并确定细胞类型。（例如树突状细胞、肺泡巨噬细胞、CD4+ T细胞），并确定长期暴露于废气对小鼠动脉粥样硬化发展的影响，特别关注动物年龄和性别的调节。这些方法将使人们深入了解弱势群体（妇女和老年人）的易感性以及干预和治疗方法。 公共卫生关系：生物柴油被吹捧为能源独立的重要战略，以及农业生产和减少运输部门对环境影响的可持续性，但与石油柴油一样，生物柴油的燃烧会产生颗粒空气污染。据报道，空气中颗粒物（PM）对健康的不利影响出乎意料地低浓度，导致科学家和公共卫生官员得出结论，长期暴露于燃烧相关的颗粒空气污染是心脏和肺部疾病的重要环境风险因素。尽管人们相信生物燃料可能对环境和人类健康更好，关于生物柴油排放物的生物效应的信息非常有限，因此本提案将比较和对比石油燃烧产生的排放颗粒的生物效应，以及年龄和性别对这些反应的影响，以便为旨在阐明这些机制的未来研究奠定基础。负责空气中PM与肺和心脏病之间的重要关系，并制定方法，以减少空气污染对健康的不利影响。