Enhancement of Coronary Constriction by Volatile Organic Air Toxics

挥发性有机空气毒物增强冠状动脉收缩

• 批准号: 9029064
• 负责人: Matthew J Campen
• 金额: $ 37.83万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9029064
• 关键词: Air; Air Pollutants; Air Pollution; Antioxidants; Apoproteins; Automobile Driving; Biological Assay; Biological Markers; Biosensor; Blood Circulation; Blood Pressure; Blood Vessels; Breathing; Carbon; Cardiopulmonary; Cardiovascular Diseases; Cardiovascular system; Cell Adhesion Molecules; Chemical Exposure; Coronary; Coronary artery; Development; Endothelial Cells; Endothelium; Environmental Health; Epidemiologic Studies; Etiology; Exhalation; Exhibits; Exposure to; Filtration; Fractionation; Functional disorder; Gases; Generations; Grant; Health; Health Benefit; High Density Lipoproteins; Hour; Human; Individual; Inflammation; Inflammatory; Inflammatory Response; Interleukin-8; Link; Lipid Peroxidation; Lipids; Lipoproteins; Literature; Lung; Measurement; Mediating; Mediator of activation protein; Modification; Motor Vehicles; Nitric Oxide; Outcome; Oxidative Stress; Parents; Particulate; Particulate Matter; Phase; Physiologic pulse; Plasma; Polyunsaturated Fatty Acids; Prevalence; Proteomics; Public Health; Reactive Oxygen Species; Regulation; Reporting; Research Personnel; Rodent; Role; Serum; Source; Sputum; Study of serum; Techniques; Testing; Toxic effect; Ultrafine; Vascular Cell Adhesion Molecule-1; Vascular Diseases; Vascular Endothelial Cell; Vehicle Emissions; Work; atherogenesis; cardiovascular health; chemokine; circulating biomarkers; constriction; exposed human population; high density lipoprotein-1; human subject; innovation; intercellular cell adhesion molecule; interest; metabolomics; novel; oxidation; particle; pollutant; public health relevance; response; scavenger receptor; stem; trafficking; volunteer

 DESCRIPTION (provided by applicant): The impact of air pollution on cardiopulmonary health is well documented. Recently, a number of epidemiological studies have reported a potential role for vehicular sources of air pollution as a major contributor to cardiovascular disease. Unfortunately, there is a lack of comprehensive human cardiovascular toxicity information for fresh vehicle emissions from which to establish causality, identify vulnerable individuals, and refine protective regulations. In the Parent R01, we have observed that freshly generated particulate matter may have a greater physical association with volatile and semi-volatile organic species, and that such particles may be more toxic to the cardiovascular system. The implications of this phenomenon may mean public health outcomes might not simply be determined by high levels of emissions, but also by proximity to the origins of those components. This ViCTER Proposal aims to expand the Parent R01 grant in two directions, namely using human exposure studies and examining the potential role for dysfunctional high-density lipoprotein to mediate systemic cardiovascular health effects. In Project 1, with Drs. Armijos and Olvera at UTEP, we will conduct a real-world exposure scenario to test the gas-particle interaction concept in human subjects. In Project 2, with Dr. Araujo at UCLA, we will expand beyond proteomic exploration of the serum and study lipids and lipoprotein modifications, and the resultant bioactivity changes caused by exposures, both in the ongoing rodent studies, and also with the proposed human exposures. Lastly, in Project 3, with Dr. Campen at UNM, we will explore the endothelial inflammatory potential of serum from the exposed humans, which will provide a crucial pathophysiological link between the real-world exposures in Project 1 and the HDL modifications and lipid peroxidation assessed in Project 2. Collectively, these Projects will test our hypothesis that VOC-rich PM will be more toxic than the carbon core of traffic-derived PM, in terms of driving circulating inflammatory potential and HDL dysfunction. This grant will incorporate the expertise of four investigators with complementary expertise and focused interest in Border Environmental Health, Drs. Araujo, Armijos, Campen, and Olvera. Outcomes will bridge ongoing toxicological and translational work being conducted among the groups. Study results will help identify regional PM/gas contrasts and airshed compositions that may be specifically deleterious to human health. Additionally we will characterize the pathophysiological role for modified HDL in mediating the systemic vascular effects of inhaled pollutants, which will provide vital information on vulnerability of specific subpopulations.

 描述（由适用提供）：空中污染对心肺健康的影响已得到充分记录。最近，许多流行病学研究报道了汽车污染源的潜在作用，这是导致心血管疾病的主要贡献者。不幸的是，缺乏针对新鲜车辆排放的全面人类心血管毒性信息，以确定因果关系，确定弱势群体并完善受保护的法规。在母体R01中，我们观察到，新鲜产生的颗粒物可能与挥发性和半挥发性有机物质具有更大的物理关联，并且这种颗粒可能对心血管系统更具毒性。这种现象的含义可能意味着公共卫生结果可能不仅仅是由高水平的排放量确定，而且还取决于靠近这些组成部分的起源。该Victer提案旨在将父级R01赠款扩展到两个方向上，即使用人类暴露研究并检查功能障碍高密度脂蛋白的潜在作用，以介导系统性心血管健康效应。在项目1中，Drs。在UTEP的Armijos和Olvera，我们将进行现实世界中的暴露情况，以测试人类受试者中的气体相互作用概念。在项目2中，随着UCLA的Araujo博士，我们将扩展超出对血清和研究脂质和脂蛋白修饰的蛋白质组学探索，以及在正在进行的啮齿动物研究中造成的曝光引起的生物活性变化，以及与拟议的人类曝光有关。最后，在项目3中，与Campen博士在UNM中，我们将探索血清中暴露的人体的内皮炎症潜力，这将在项目1中的现实世界暴露与HDL修改中的现实世界暴露与HDL修改中的现实世界暴露之间存在至关重要的病理生理联系。驱动循环感染潜力和HDL功能障碍的术语。该赠款将纳入四名具有完全专业知识的调查人员的专业知识，并对边境环境健康的兴趣集中，Drs。 Araujo，Armijos，Campen和Olvera。结果将弥合正在进行的毒理学和群体中进行的翻译工作。研究结果将有助于确定可能专门删除人类健康的区域性PM/气体对比度和空影组合物。此外，我们将表征改进的HDL在介导遗传污染物的全身血管效应中的病理生理作用，该血管的系统性血管作用将提供有关特定亚群脆弱性的重要信息。