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

基本信息

批准号：
7808215
负责人：
NAOMI K FUKAGAWA
金额：
$ 50万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-28 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7808215
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

项目摘要

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1970年代以来，已经报道了不良健康的颗粒空气污染水平，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一项重大心脏和肺部疾病的环境风险因素。尽管大量研究研究了石油柴油（石油）排气排放对呼吸系统的影响，但导致报告的不良人类健康效应的机制，并确定了颗粒物的有毒引发物种仍然难以捉摸。由植物油或动物脂肪制成的生物柴油燃料正在获得动力，这是美国和欧洲未来的能源。生物柴油通常将其混合到常规的柴油燃料中，并且发射测试表明，生物柴油排放似乎包含碳氢化合物水平降低，一氧化碳和颗粒物（PM），但在颗粒相中，较高的溶解有机分数。据报道，促进年龄是动脉粥样硬化的已知危险因素，并且已经报道了心血管疾病（CVD），自身免疫性疾病和气道超敏反应的性别差异。越来越多的证据表明空气污染物会加剧CVD，重要的是确定导致动脉粥样硬化加剧的机制以及年龄和性别对对基础CVD上吸入颗粒的反应的影响。要检验的假设是，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。这最终将导致动脉粥样硬化的加重程度，这将受动物的年龄和性别调节。该建议将建立用于吸入研究的发动机排放的受控生产。排气的颗粒和气态成分以及与臭氧反应后的异质氧化产物的表征。使用疾病的动物模型，我们将在3天和9天暴露于发动机排气以及特定气体和颗粒物尺寸的局部疾病后识别肺中的关键信号通路和炎症反应，量化并确定细胞的类型（例如，树突状细胞，肺泡，肺泡细胞暴露于发动机排气后诱导的巨噬细胞，CD4+ T细胞），并确定长期暴露于排气的影响小鼠动脉粥样硬化的发展，其特定侧重于动物的年龄和性别。这些方法将洞悉弱势群体（妇女和老年人）的敏感性以及干预和治疗方法。公共卫生相关性：生物柴油已被吹捧为能源独立性以及在农业生产方面的可持续性的重要策略，并减少了运输部门的环境影响，但是与石油柴油一样，生物柴油的燃烧会产生颗粒空气污染。据报道，空气中颗粒物物质（PM）的不良健康影响在意外的低浓度下，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。尽管认为生物燃料可能对环境和人类健康更好，但关于生物柴油排放的生物学影响的信息非常有限，因此该建议将比较和对比发射颗粒的生物学作用，从而对石化和生物柴油和生物柴油的燃烧以及年龄和性别对这些反应的影响是为了为未来的研究奠定基础。