Combustion-Generated EPFRs: Assessing Cardiovascular Risks of Exposure
燃烧产生的 EPFR:评估暴露的心血管风险
基本信息
- 批准号:10576461
- 负责人:
- 金额:$ 28.87万
- 依托单位:
- 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:2009-08-15 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAgonistAirAirborne Particulate MatterAlveolarArchivesAryl Hydrocarbon ReceptorBindingBiological MarkersBloodBlood PressureBlood VesselsCardiacCardiopulmonaryCardiovascular DiseasesCardiovascular systemCathetersCollaborationsCommunitiesComplementDataData AnalysesDevelopmentDevicesEndothelial CellsEndotheliumEnvironmentEpithelial CellsEpitheliumExposure toFree RadicalsFunctional disorderHazardous WasteHealthHeartHeart DiseasesHistologyIndustrializationInhalationInhalation ExposureInhalation ToxicologyInjuryKnowledgeLeftLeft Ventricular FunctionLigandsLinkLipidsLungMass Spectrum AnalysisMeasuresMediatingMediatorMembraneMembrane LipidsModelingMorphologyMusMyocardial dysfunctionOxidation-ReductionOxidative StressParticulate MatterPhysiologic intraventricular pressurePhysiologicalPlayPulmonary Vascular ResistanceReactive Oxygen SpeciesReceptor ActivationResearchRiskRisk AssessmentRodentRoleSecondary toSignal Recognition ParticleSiteSoilSourceSuperfundSystemTechnologyTelemetryTestingTissuesToxic effectVascular DiseasesVentricularWorkair filteralveolar epitheliumaryl hydrocarbon receptor ligandbiological systemsbody systemcardiovascular risk factordata managementdesignendothelial dysfunctionenvironmental chemistryepidemiologic datafree radical oxygenheart functionlung pressuremortalitynoveloxidationoxidized lipidparticlepollutantpressurepulmonary arterial pressureremediationresponsesmall moleculesuperfund siteuptakevascular injuryweb portal
项目摘要
Project Summary/Abstract: Project 2
Particulate matter (PM) is consistently associated with cardiopulmonary and cardiovascular mortality. Despite
the risk of exposure, little is known about the mechanisms underlying PM-mediated toxicity. Our Center has
shown that PM emissions from the thermal treatment (TT) of hazardous organics or contaminated soils at
Superfund sites produce environmentally persistent free radicals (EPFRs). EPFRs are a unique particle-
pollutant system capable of redox cycling to generate reactive oxygen species (ROS) in biological systems.
EPFRs are present in contaminated Superfund soils and airborne PM near industrialized Superfund sites. Our
prior Superfund project focused on the role of EPFRs in modulating cardiac function and disease. Although
inhalation of EPFRs decreased baseline cardiac function, we found that these effects were secondary to
changes in pulmonary vascular resistance. The mechanism(s) underlying these vascular effects are unknown;
however, our preliminary data suggest that EPFR-mediated activation of the aryl hydrocarbon receptor (AhR)
in pulmonary epithelial cells resulting in the release of vasoactive factors may play an important
pathophysiological role. Our central hypothesis is that EPFR-mediated activation of AhR at the air-blood
interface and mobilization of vasoactive mediators leads to activation/dysfunction of the pulmonary and
systemic vasculature, resulting in cardiovascular disease. To test this hypothesis, Specific Aim 1 will test
whether EPFR-mediated activation of the AhR in lung epithelium is responsible for the increase in pulmonary
pressure and decreased diastolic filling that underlies EPFR induced cardiac dysfunction. After establishing the
vasculature as the locus of injury, Specific Aim 2 will elucidate the cellular mechanisms of vascular injury by
testing whether EPFRs induce vascular dysfunction via activation of the AhR. In both aims, control littermate
mice and mice deficient in AhR specifically in alveolar type II will be exposed subchronially to EPFRs, non-
EPFR PM, or filtered air using a recently designed inhalation system. Millar pressure-volume catheters will be
used to measure left ventricular function and pulmonary arterial pressure in exposed mice. Telemetry devices
will be used to record blood pressure. Endothelium-dependent vascular reactivity, as well as markers for both
endothelial dysfunction and activation, will be assessed. Specific Aim 3 will identify a putative ligand promoting
EPFR-induced AhR activation and test whether this metabolite is associated with EPFR-mediated vascular
dysfunction. In collaboration with Project 1, this aim will use novel mass spectrometry approaches to identify
and characterize EPFR-induced lipid oxidation products that may serve as endogenous AhR agonists so that
we may correlate tissue and blood levels of these metabolites with vascular dysfunction. Completion of these
Aims will provide important new data linking EPFR-mediated oxidative stress in epithelial cells, AhR activation,
and cardiovascular disease. This information is critical for assessing risks to those living in proximity to sites
using TT technologies to remediate Superfund or other hazardous wastes.
项目摘要/摘要:项目2
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('TAMMY R DUGAS', 18)}}的其他基金
Novel coatings releasing synergistic polyphenols promote vascular healing
新型涂层释放协同多酚促进血管愈合
- 批准号:
8918078 - 财政年份:2014
- 资助金额:
$ 28.87万 - 项目类别:
Novel coatings releasing synergistic polyphenols promote vascular healing
新型涂层释放协同多酚促进血管愈合
- 批准号:
8716232 - 财政年份:2014
- 资助金额:
$ 28.87万 - 项目类别:
Research Experience and Training Coordination Core (RETCC)
研究经验和培训协调核心(RETCC)
- 批准号:
10341189 - 财政年份:2009
- 资助金额:
$ 28.87万 - 项目类别:
Combustion-Generated EPFRs: Assessing Cardiovascular Risks of Exposure
燃烧产生的 EPFR:评估暴露的心血管风险
- 批准号:
10341193 - 财政年份:2009
- 资助金额:
$ 28.87万 - 项目类别:
Antiretroviral Therapy, Endothelial Dysfunction and Atherosclerosis
抗逆转录病毒治疗、内皮功能障碍和动脉粥样硬化
- 批准号:
7838921 - 财政年份:2009
- 资助金额:
$ 28.87万 - 项目类别:
Research Experience and Training Coordination Core (RETCC)
研究经验和培训协调核心(RETCC)
- 批准号:
10576457 - 财政年份:2009
- 资助金额:
$ 28.87万 - 项目类别:
Combustion-Generated EPFRs: Assessing Cardiovascular Risks of Exposure
燃烧产生的 EPFR:评估暴露的心血管风险
- 批准号:
10116407 - 财政年份:2009
- 资助金额:
$ 28.87万 - 项目类别:
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