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 20 世纪 70 年代以来，据报道，颗粒物空气污染水平出乎意料地低，对健康产生了不利影响，这使得科学家和公共卫生官员得出结论，长期暴露于与燃烧相关的细颗粒物空气污染对健康产生了重大影响。心脏病和肺病的环境危险因素。尽管有大量研究考察了石油柴油（石化柴油）废气排放对呼吸系统的影响，但造成所报告的人类健康不良影响的机制以及查明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燃料作为未来能源的势头正在增强。生物柴油通常与传统柴油燃料混合，排放测试表明，生物柴油排放物中碳氢化合物、一氧化碳和颗粒物 (PM) 的含量似乎有所减少，但颗粒相中的可溶性有机部分含量较高。年龄增长是动脉粥样硬化的已知危险因素，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有报道。随着越来越多的证据表明空气污染物会加剧CVD，确定导致动脉粥样硬化恶化的机制以及年龄和性别对吸入颗粒对潜在CVD反应的影响非常重要。要测试的假设是，与石化柴油燃烧相比，生物柴油排放的颗粒物和气体排放物在肺损伤和不良全身炎症反应的程度方面会有所不同。这最终将导致动脉粥样硬化不同程度的恶化，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。废气中的颗粒和气态成分以及与臭氧反应后的非均相氧化产物将被表征。使用疾病动物模型，我们将确定暴露于发动机废气和特定气体和颗粒尺寸部分 3 天和 9 天后肺部的关键信号传导途径和炎症反应，量化并确定细胞类型（例如树突状细胞、肺泡细胞）。暴露于发动机废气后诱导的巨噬细胞、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，特别关注年龄和性别的调节的动物。这些方法将深入了解弱势群体（妇女和老年人）的易感性以及干预和治疗方法。公共健康相关性：生物柴油被认为是能源独立、农业生产可持续性和减少运输部门对环境影响的重要战略，但与石化柴油一样，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) 的浓度出乎意料地低，对健康产生不利影响，这使得科学家和公共卫生官员得出结论，长期暴露于与燃烧相关的颗粒物空气污染是导致心脏和肺部疾病的一个重要环境风险因素。尽管人们相信生物燃料可能对环境和人类健康更好，但有关生物柴油排放的生物效应的信息非常有限，因此该提案将比较和对比石油和生物柴油燃烧产生的排放颗粒的生物效应年龄和性别对这些反应的影响，旨在为未来的研究奠定基础，旨在阐明空气中的颗粒物与肺部和心脏病之间的重要关系的机制，并制定减少空气污染对健康造成的不利影响的方法。