Ambient Particle Composition and Vascular Dysfunction
环境颗粒成分和血管功能障碍
基本信息
- 批准号:8011702
- 负责人:
- 金额:$ 2.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-01-01 至 2012-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcetylcholineAcetylcysteineAcuteAddressAdhesionsAdverse effectsAgonistAirAir PollutionAirborne Particulate MatterAntioxidantsAspirate substanceAutomobile DrivingBiologicalBiological AvailabilityBlood CirculationBlood VesselsBreathingCalciumCellsChemicalsCitiesCyclooxygenase InhibitorsDataDepositionDiesel ExhaustDiscriminationDoseEndothelial CellsEndotheliumEnzymesEpithelialEpithelial CellsExcisionExposure toFoundationsFunctional disorderGene ExpressionGenerationsGeographic LocationsGermanyGlutathioneGoalsHealthHeart DiseasesHumanIL8 geneImmuneInflammationInflammation MediatorsInflammatoryInflammatory ResponseInterleukin-6Knock-outKnockout MiceKnowledgeLaboratoriesLeadLiteratureLocationLungLymphaticLysosomesMeasurementMeasuresModelingMucociliary ClearanceMusNickelNitric OxideNitric Oxide SynthaseOralOxidative StressParticle SizeParticulate MatterPathway interactionsPneumoniaProcessProductionPublic HealthReactive Oxygen SpeciesReportingResearchRespiratory SystemRespiratory tract structureRiskRoleSamplingSourceTNF geneTestingTissuesToxic effectTransgenic ModelUltrafineVascular SystemWild Type MouseWorkambient particlebasebiological adaptation to stressbiological systemscardiovascular disorder riskchemical reactioncytotoxicityextracellularhuman NOS3 proteinin vivomacrophagemouse modelneutrophiloil fly ashparticlepreventrespiratoryresponseultrafine particle
项目摘要
DESCRIPTION (provided by applicant): Recent studies suggest that particulate matter (PM) derived from different sources with necessarily different physicochemical make up may differ in toxicity. It is important to investigate what components impact human health to assist the regulatory agencies to impose emission standards to reduce the health risk. The goal of this study is to use collected and characterized fine ambient particles, to determine the in vivo systemic vascular dysfunction in a murine model. Particles have been collected over the period of one month from 10 cities within the U.S. and 2 that are in Germany, (Hettstedt and Zerbst). Preliminary data on size and particle composition, as well as cellular response studies that focus on oxidative stress have been completed in our laboratory; these data will be utilized as our foundation for this study. Wild type (WT) and endothelial nitric oxide synthesis knockout (eNOS -/-) mice will be exposed, via trans-oral aspiration, to single or repeated doses of coarse, fine, and ultrafine particles from these locations to determine radical oxidative species formation and subsequent inflammation response and vascular dysfunction. We hypothesize that PM-induced pulmonary inflammation leads to uncoupling of eNOS in the systemic vasculature, which in turn will lead to NOS-generated intracellular radical oxidative stress (ROS). Intracellular oxidative stress induced by PM exposure causes endothelial nitric oxide synthesis inhibition and increases neutrophil adhesion to endothelial cells, causing inflammatory damage. The inflammation-related responses can then be correlated to vascular dysfunction by measuring polymorphonuclear leukocytes (PMN) in the lung in comparison to measurements of PMN in the circulation in WT vs. eNOS -/- mice. The characterization of systemic insult will be assessed by comparing vascular markers of oxidative stress (iNOS, eNOS activities and gene expression, glutathione levels, etc) and dysfunction (contraction response to agonists) in eNOS -/- to WT mice. Usage of the eNOS -/- mice will aid in understanding the mechanisms behind this uncoupling and, to verify this ROS generating pathway.
描述(由申请人提供):最近的研究表明,粒子物质(PM)来自具有不同物理化学构成的不同来源的毒性可能有所不同。重要的是要研究哪些组成部分影响人类健康,以帮助监管机构施加排放标准以降低健康风险。这项研究的目的是使用收集的并表征精细的环境颗粒,以确定鼠模型中体内全身性血管功能障碍。从美国的10个城市和德国的2个城市(Hettstedt和Zerbst)收集了一个月的一个月。有关大小和颗粒组成的初步数据,以及针对氧化应激的细胞反应研究,我们的实验室已经完成;这些数据将被用作我们的这项研究的基础。野生型(WT)和内皮氮氧化物合成基因敲除(ENOS - / - )小鼠将通过反式口吸吸入暴露于这些位置的粗,细和超型颗粒的单剂量或重复剂量,以确定自由基氧化物质形成,并随后的炎症反应以及随后的炎症反应和血管造成的功能障碍。我们假设PM诱导的肺部炎症会导致全身性脉管系统中eNOS的解偶,这又会导致NOS生成的细胞内自由基氧化应激(ROS)。由PM暴露诱导的细胞内氧化应激会导致内皮一氧化氮的合成抑制,并增加中性粒细胞对内皮细胞的粘附,从而导致炎症损伤。与肺中PMN的测量值相比,与肺部的PMN相比,与肺部的循环相比,可以通过测量肺中的多形核白细胞(PMN)来将与炎症相关的反应与血管功能障碍相关。将通过比较氧化应激(INOS,eNOS活性和基因表达,谷胱甘肽水平等)和功能障碍(对激动剂的收缩反应)与WT小鼠的功能障碍(对激动剂的收缩反应)来评估全身性损伤的表征。 eNOS - / - 小鼠的使用将有助于理解这种解偶联背后的机制,并验证这种ROS产生途径。
项目成果
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Azita K. Madrid-Cuevas其他文献
Azita K. Madrid-Cuevas的其他文献
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{{ truncateString('Azita K. Madrid-Cuevas', 18)}}的其他基金
Ambient Particle Composition and Vascular Dysfunction
环境颗粒成分和血管功能障碍
- 批准号:
8208150 - 财政年份:2010
- 资助金额:
$ 2.58万 - 项目类别:
Ambient Particle Composition and Vascular Dysfunction
环境颗粒成分和血管功能障碍
- 批准号:
7810213 - 财政年份:2010
- 资助金额:
$ 2.58万 - 项目类别:
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