The Role of the KLF2 in Vascular Endothelial Cells
KLF2 在血管内皮细胞中的作用
基本信息
- 批准号:7743732
- 负责人:
- 金额:$ 39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-01-19 至 2012-06-30
- 项目状态:已结题
- 来源:
- 关键词:AblationAffinity ChromatographyAnimal ModelAnimalsAortaAreaAtherosclerosisBindingBiological AssayBiologyBiomechanicsBlood PressureBlood VesselsBreedingCellular biologyCloningCoronary heart diseaseCoupledDNADevelopmentElectrophoretic Mobility Shift AssayElementsEndothelial CellsEndotheliumExhibitsFaceFibrinogenGene ExpressionGene Expression RegulationGenesGenetic PolymorphismGoalsHealthHumanIn VitroIntegrinsInvestigationKnock-outKnockout MiceKruppel-like transcription factorsLaboratoriesLesionLightLiquid substanceLungMass Spectrum AnalysisMeasurementMeasuresMediatingMethodsModelingMolecularMusNatureNuclearPathway interactionsPatternPhenotypePhysiologicalPlayPredispositionProceduresProductionPropertyRegulationRelaxationRoleSerologicalSeveritiesSignal Transduction PathwaySiteSmall Interfering RNAStimulusTelemetryTestingTransgenic MiceTransgenic OrganismsUp-RegulationVascular Endothelial CellVascular Endothelial Growth Factor Receptor-2VasodilationWorkathero susceptiblebiological adaptation to stresschromatin immunoprecipitationdefined contributionfluid flowgenetic risk factorin vivoknockout animalmouse modelnew therapeutic targetpromoterresearch studyresponseshear stresstherapeutic targettranscription factor
项目摘要
The overall goal of these studies is to define the mechano-induction and function of the endothelial KLF2
transcription factor in vascular biology. Our laboratory has performed numerous studies that have
contributed significantly to understanding KLF2. These include the original cloning of the KLF2 gene, the
development and examination of animals lacking KLF2 expression, and the initiation of studies on the
regulation of the endothelial KLF2 gene by fluid shear stress. KLF2 plays an important role in endothelial
cell (EC) biology. In vitro and in vivo experiments with human and mouse vascular ECs indicate that KLF2
exhibits sustained induction under pulsatile laminar shear stress, a biomechanical stimulus with recognized
vaso-protective properties. Furthermore, numerous in vitro studies have demonstrated that KLF2 gene
expression has the potential to reduce the susceptibility of the endothelium to atherosclerosis. We
hypothesize that KLF2 mediates athero-protective endothelial phenotypes and, as such, that the
mechanisms leading to KLF2 expression represent important therapeutic targets. These studies will expand
upon our previous work on the mechano-transduction pathways responsible for the upregulation of KLF2
expression in response to fluid flow. They will also be the first to test whether KLF2 expression is sufficient
to decrease the severity of lesions in murine models of atherosclerosis. Additionally, they will define the
contribution of KLF2 to vasodilation in vivo using conditional knockout and transgenic over-expressing
murine animal models. Importantly, they will serve as a prerequisite for further investigation of KLF2 as a
vaso-protective therapeutic target.
这些研究的总体目标是确定内皮KLF 2的机械诱导和功能。
血管生物学中的转录因子。我们的实验室进行了大量的研究,
对理解KLF2有很大贡献。这些包括KLF2基因的原始克隆,
缺乏KLF2表达的动物的开发和检查,以及启动对
通过流体剪切应力调节内皮KLF2基因。KLF2在血管内皮细胞增殖中起重要作用。
细胞(EC)生物学。人和小鼠血管内皮细胞的体外和体内实验表明,KLF2
在脉动层流剪切应力下表现出持续的诱导,这是一种公认的生物力学刺激,
血管保护特性。此外,许多体外研究表明,KLF2基因
表达具有降低内皮对动脉粥样硬化的易感性的潜力。我们
假设KLF2介导动脉粥样硬化保护内皮表型,因此,
导致KLF2表达的机制代表了重要的治疗靶点。这些研究将扩大
基于我们之前对KLF2上调的机械转导通路的研究,
响应于流体流动的表达。他们也将是第一个测试KLF2表达是否足够的人。
以降低动脉粥样硬化小鼠模型中病变的严重程度。此外,他们将定义
利用条件性敲除和转基因过表达研究KLF2对血管舒张的作用
鼠动物模型。重要的是,它们将作为进一步调查KLF 2的先决条件。
血管保护治疗靶点。
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('JERRY B LINGREL', 18)}}的其他基金
The Role of the KLF2 in Vascular Endothelial Cells
KLF2 在血管内皮细胞中的作用
- 批准号:
7341585 - 财政年份:2007
- 资助金额:
$ 39万 - 项目类别:
The Role of the KLF2 in Vascular Endothelial Cells
KLF2 在血管内皮细胞中的作用
- 批准号:
7541782 - 财政年份:2007
- 资助金额:
$ 39万 - 项目类别:
The Role of the KLF2 in Vascular Endothelial Cells
KLF2 在血管内皮细胞中的作用
- 批准号:
7209132 - 财政年份:2007
- 资助金额:
$ 39万 - 项目类别:
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