Cerebrovascular Atherosclerosis: Genes & Gene Expression
脑血管动脉粥样硬化:基因
基本信息
- 批准号:7176068
- 负责人:
- 金额:$ 16.81万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-02-25 至 2010-01-31
- 项目状态:已结题
- 来源:
- 关键词:AgeAgingAmericanAnimal ModelAnimalsArachidonate 12-LipoxygenaseArachidonate 15-LipoxygenaseArterial Fatty StreakAtherosclerosisBioinformaticsBlood VesselsCandidate Disease GeneCase-Control StudiesCephalicCerebrovascular DisordersCerebrumCessation of lifeCharacteristicsCholesterolCodeCollaborationsComplexConditionCore FacilityDNADataDevelopmentDiabetes MellitusDiseaseEducationEnvironmentEvolutionExposure toExtramural ActivitiesFamily suidaeFutureGene ExpressionGene ProteinsGenesGeneticGenetic Predisposition to DiseaseGenetic VariationGenomicsGoalsHealthHereditary DiseaseHumanHyperlipidemiaInflammationInflammatoryInflammatory ResponseInjuryInstitutesInsulinInterleukin-1InterventionIntracranial AtherosclerosesKnowledgeLeadLiteratureMediator of activation proteinMembraneMentorsMicroarray AnalysisModelingMolecularMonocyte Chemoattractant Protein-1Monocyte Chemoattractant ProteinsNeurologicNormal tissue morphologyOutcomePathogenesisPathway interactionsPhysiciansPlayPredispositionPreventionPreventive InterventionPrincipal InvestigatorProteinsProteomicsRangeRecurrenceResearchResearch PersonnelResourcesReverse Transcriptase Polymerase Chain ReactionRiskRisk FactorsRoleSeveritiesStagingStratificationStrokeSus scrofaTestingTherapeuticTherapeutic InterventionTimeTissuesTrainingUniversitiesValidationVirginiaWorkanakinraatherogenesisbasecareercerebrovasculardiabeticdisabilitydisorder preventionexperiencehuman diseaseimprovedinnovationnovelnovel diagnosticspreventprogramsprotein expressionresearch studyresponse to injurysuccess
项目摘要
DESCRIPTION (provided by applicant): Over 780,000 strokes occur annually in the U.S. with at least 125,000 directly related to large vessel cerebrovascular atherosclerosis. Atherosclerosis is a complex genetic disease in which diabetes, hyperlipidemia and other vascular risk factors result in endothelial injury leading to an inflammatory response. Although the general inflammatory cascade has been described, specific pathophysiological mediators of the response-to-injury mechanisms in atherogenesis are not known. Identification of genes and pathways involved in atherosclerosis in an established porcine model of atherosclerosis is expected to elucidate the pathogenesis of human atheroselerosis and lead to specific therapeutic interventions that reduce the burden of cerebrovascular disease. Our central hypothesis is that genes coding for pro- and counter-inflammatory mediators will be differentially expressed in atherosclerotic and pre-atherosclerotic cerebral vessels compared with normal vessels favoring a pro-inflammatory protein profile. The Specific Aims of this proposal are to 1) Characterize a new large animal model of carotid and intracranial atherosclerosis, the diabetic/hyperlipemic pig simultaneously testing the effect of insulin treatment on atherosclerosis, 2) identify the genomic, proteomic and functional activities of key mediator molecules during the cerebrovascular atherogenesis (12 lipoxygenase, interleukin-1 receptor antagonist and monocyte chemotactic protein-I), and 3) identify differentially expressed genes in atherosclerotic, pre-atherosclerotic, and normal cerebral and precerebral vessels. The training goals are to broaden the principal investigator's education in basic stroke research on inflammatory and genetic mechanisms, to develop his expertise in gene expression and molecular basis of atherosclerosis, and to facilitate his development of a research team. Upon completion, we expect to have narrowed the range of candidate inflammatory genes associated with cerebrovascular atherosclerosis and related to vascular risk factors. This data will allow informed selection of candidate genes for future case-control studies. Collectively, these outcomes will associate previously suspected and novel inflammatory mediators with atherogenesis and plaque progression providing potential targets for treatment of this disease and prevention of its devastating complications, including stroke.
描述(申请人提供):美国每年发生超过780,000例中风,其中至少125,000例与大血管脑血管动脉粥样硬化直接相关。动脉粥样硬化是一种复杂的遗传性疾病,糖尿病、高脂血症和其他血管危险因素导致内皮损伤,导致炎症反应。虽然已经描述了一般的炎性级联反应,但动脉粥样硬化形成中损伤反应机制的特定病理生理介质尚不清楚。在已建立的猪动脉粥样硬化模型中识别参与动脉粥样硬化的基因和途径有望阐明人类动脉粥样硬化的发病机制,并导致特定的治疗干预措施,以减轻脑血管疾病的负担。我们的中心假设是,与正常血管相比,编码促炎和抗炎介质的基因将在动脉粥样硬化和动脉粥样硬化前的脑血管中差异表达,从而有利于促炎蛋白的表达。这一建议的具体目的是:1)建立一种新的颈动脉和颅内动脉粥样硬化的大型动物模型,糖尿病/高脂血症猪同时测试胰岛素治疗对动脉粥样硬化的影响;2)鉴定脑血管动脉粥样硬化形成过程中关键介质分子(12脂氧合酶、白细胞介素1受体拮抗剂和单核细胞趋化蛋白-I)的基因组、蛋白质组和功能活性;3)鉴定动脉粥样硬化、动脉粥样硬化前病变和正常脑及前脑血管中差异表达的基因。培训的目标是扩大首席研究员在基础中风研究炎症和遗传机制方面的教育,发展他在动脉粥样硬化的基因表达和分子基础方面的专业知识,并促进他发展研究团队。完成后,我们预计将缩小与脑血管动脉粥样硬化和血管危险因素相关的候选炎症基因的范围。这些数据将允许在知情的情况下为未来的病例对照研究选择候选基因。总而言之,这些结果将把以前怀疑的和新型的炎症介质与动脉粥样硬化和斑块进展联系起来,为治疗这种疾病和预防包括中风在内的破坏性并发症提供潜在的靶点。
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('BRADFORD B WORRALL', 18)}}的其他基金
Gastrointestinal Microbiome and Stroke Outcomes Network (GEMSTONE)
胃肠道微生物组和中风结果网络 (GEMSTONE)
- 批准号:
9792290 - 财政年份:2018
- 资助金额:
$ 16.81万 - 项目类别:
Cerebrovascular Atherosclerosis: Genes & Gene Expression
脑血管动脉粥样硬化:基因
- 批准号:
7020667 - 财政年份:2005
- 资助金额:
$ 16.81万 - 项目类别:
Cerebrovascular Atherosclerosis: Genes & Gene Expression
脑血管动脉粥样硬化:基因
- 批准号:
7561026 - 财政年份:2005
- 资助金额:
$ 16.81万 - 项目类别:
Cerebrovascular Atherosclerosis: Genes & Gene Expression
脑血管动脉粥样硬化:基因
- 批准号:
6869201 - 财政年份:2005
- 资助金额:
$ 16.81万 - 项目类别:
Cerebrovascular Atherosclerosis: Genes & Gene Expression
脑血管动脉粥样硬化:基因
- 批准号:
7414470 - 财政年份:2005
- 资助金额:
$ 16.81万 - 项目类别:
Phenotype core - The NINDS International Stroke Genetics Consortium Study
表型核心 - NINDS 国际中风遗传学联盟研究
- 批准号:
8282863 - 财政年份:
- 资助金额:
$ 16.81万 - 项目类别:
Phenotype core - The NINDS International Stroke Genetics Consortium Study
表型核心 - NINDS 国际中风遗传学联盟研究
- 批准号:
8046524 - 财政年份:
- 资助金额:
$ 16.81万 - 项目类别:
Phenotype core - The NINDS International Stroke Genetics Consortium Study
表型核心 - NINDS 国际中风遗传学联盟研究
- 批准号:
8479449 - 财政年份:
- 资助金额:
$ 16.81万 - 项目类别:
Phenotype core - The NINDS International Stroke Genetics Consortium Study
表型核心 - NINDS 国际中风遗传学联盟研究
- 批准号:
8375358 - 财政年份:
- 资助金额:
$ 16.81万 - 项目类别:
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