Mechanisms of neovascularization in response to ischemia
Mechanisms of neovascularization in response to ischemia
批准号:
9086396
负责人:
Victoria L Bautch
金额:
$37.57万
依托单位国家:
美国
项目类别:
财政年份:
2014
资助国家:
美国
项目状态:
已结题
起止时间:
2014-08-01 至 2018-05-31
关键词:
Adaptor Signaling ProteinArchitectureArteriosclerosisBindingBlood typing procedureCardiovascular DiseasesCardiovascular PhysiologyCell ProliferationCell physiologyCellsCholesterolCollagenComplexCoupledDataDevelopmentDiseaseEndothelial CellsEnvironmentFluorescenceFluorescence Resonance Energy TransferGleanGrowthHealthHindlimbImage AnalysisIn VitroInflammationIntegrinsIschemiaKDR geneLeadLigationLiquid substanceMechanicsMediatingModelingMolecularMusPatientsPerfusionPeripheral Vascular DiseasesPositioning AttributeProcessProtein DeficiencyProteinsProteomicsPublishingRecoveryRegulationResearchRoleSignal PathwaySignal TransductionSignal Transduction PathwaySignaling ProteinStructureTestingTherapeuticTissuesTransgenic MiceTreesTyrosine PhosphorylationVascular remodelingWorkWound Healingangiogenesisbaseblood groupblood perfusionclinically relevantfemoral arterygene therapyhemodynamicshypercholesterolemiaimprovedin vitro Modelin vivoinsightmutantneovascularizationnoveloxidized low density lipoproteinpostnatalprotein activationreceptorrepairedresearch studyresponserestorationshear stresssmall moleculetherapeutic development
中文摘要
描述(由申请人提供):缺血后的新生血管形成是一个重要的修复过程,在胆固醇长期升高的情况下,这一过程受到严重损害。治疗性新生血管试验显示,高胆固醇血症患者的反应显著降低;然而,关于高胆固醇血症对动脉形成的影响的信息很少。动脉生成,即在动脉网络之间形成桥梁的侧支血管的向外重塑,对于血液灌注恢复至关重要
英文摘要
DESCRIPTION (provided by applicant): Neovascularization in response to ischemia is an important repair process, which is severely compromised in the setting of chronically elevated cholesterol. Therapeutic neovascularization trials have revealed dramatically reduced responses in hypercholesterolemic patients; however, there is little information on the effects of hypercholesterolemia on arteriogenesis. Arteriogenesis, the outward remodeling of collateral vessels that form bridges between arterial networks, is critical for recovery of blood perfusion to
the ischemic tissue after occlusion. Collateral remodeling is driven by a sudden increase in hemodynamic forces, especially shear stress, resulting from the drastic increase in flow through collaterals. This increase in shear stress is sensed by mechanosensory proteins expressed in endothelial cells (ECs), which initiate signal transduction pathways that induce processes such as cell proliferation and inflammation. Despite significant efforts to increase collateral growth and perfusion recovery in the setting of ischemia using small molecules and gene therapy approaches, results have been largely disappointing, underscoring the importance of studies on understanding the molecular mechanisms that drive arteriogenesis. Recently published work from our group, coupled with nascent observations provided in this application, identify the signaling protein adaptor protein Src homologous and collagen protein (Shc) as an essential regulator of neovascularization. To better understand the role of Shc in neovascularization, three interrelated aims are proposed. Aim 1 will determine the role of Shc in neovascularization in response to ischemia in the setting of hypercholesterolemia. Aim 2 will determine the role of Shc in endothelial mechanotransduction under defined collateral hemodynamic conditions in vitro. Aim 3 will determine the molecular determinants in Shc that facilitate neovascularization. Experiments proposed in this proposal will contribute to our understanding of molecular mechanisms of arteriogenesis and collateral remodeling. Elucidation of some of the signals that regulate post-ischemic neovascularization is needed in order to develop therapeutic strategies for diseases such as peripheral vascular disease, arteriosclerosis and wound healing.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
NAVBO Workshops at Vascular Biology 2019
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批准号:9762643
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项目类别:
-
资助金额:$3.0万
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财政年份:2019
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负责人:Victoria L Bautch
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依托单位:
MOLECULAR AND CELLULAR CONTROL OF ANGIOGENESIS
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批准号:10335185
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项目类别:
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资助金额:$92.23万
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财政年份:2018
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负责人:Victoria L Bautch
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依托单位:
MOLECULAR AND CELLULAR CONTROL OF ANGIOGENESIS
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批准号:10536676
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项目类别:
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资助金额:$92.23万
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财政年份:2018
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负责人:Victoria L Bautch
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依托单位:
Mechanisms of neovascularization in response to ischemia
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批准号:8900327
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项目类别:
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资助金额:$37.0万
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财政年份:2014
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负责人:Victoria L Bautch
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依托单位:
Centrosome Mis-Regulation and Blood Vessel Function
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批准号:8418818
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项目类别:
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资助金额:$36.18万
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财政年份:2013
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负责人:Victoria L Bautch
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依托单位:
Centrosome Mis-Regulation and Blood Vessel Function
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批准号:8701386
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项目类别:
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资助金额:$37.24万
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财政年份:2013
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负责人:Victoria L Bautch
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依托单位:
NAVBO Developmental Vascular Biology Workshop
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批准号:8209042
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项目类别:
-
资助金额:$1.8万
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财政年份:2008
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负责人:Victoria L Bautch
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依托单位:
NAVBO Developmental Vascular Biology Workshop
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批准号:7993114
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项目类别:
-
资助金额:$0.0万
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财政年份:2008
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负责人:Victoria L Bautch
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依托单位:
Integrating Cell Division and Morphogenesis in Developing Vessels
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批准号:7655236
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项目类别:
-
资助金额:$36.1万
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财政年份:2007
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负责人:Victoria L Bautch
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依托单位:
Integrating Cell Division and Morphogenesis in Developing Vessels
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批准号:7323843
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项目类别:
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资助金额:$36.12万
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财政年份:2007
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负责人:Victoria L Bautch
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依托单位:
Integrating Cell Division and Morphogenesis in Developing Vessels
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批准号:7894508
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项目类别:
-
资助金额:$36.09万
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财政年份:2007
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负责人:Victoria L Bautch
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依托单位:
"Vasculata 2007" Conference grant application
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批准号:7334644
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项目类别:
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资助金额:$1.5万
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财政年份:2007
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负责人:Victoria L Bautch
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依托单位:
Integrating Cell Division and Morphogenesis in Developing Vessels
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批准号:7499685
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项目类别:
-
资助金额:$36.11万
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财政年份:2007
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负责人:Victoria L Bautch
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依托单位:
Ras/Rap Signaling and Endothelial Morphogenesis
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批准号:7021045
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项目类别:
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资助金额:$36.19万
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财政年份:2006
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负责人:Victoria L Bautch
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依托单位:
Ras/Rap Signaling and Endothelial Morphogenesis
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批准号:7184378
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项目类别:
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资助金额:$35.14万
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财政年份:2006
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负责人:Victoria L Bautch
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依托单位:
Ras/Rap Signaling and Endothelial Morphogenesis
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批准号:7572944
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项目类别:
-
资助金额:$35.14万
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财政年份:2006
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负责人:Victoria L Bautch
-
依托单位:
Ras/Rap Signaling and Endothelial Morphogenesis
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批准号:7342131
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项目类别:
-
资助金额:$35.14万
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财政年份:2006
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负责人:Victoria L Bautch
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依托单位:
CORE--TRANSGENIC MOUSE
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批准号:6563740
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项目类别:
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资助金额:$15.75万
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财政年份:2002
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负责人:Victoria L Bautch
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依托单位:
Integrating Cell Division and Morphogenesis in Vessels
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批准号:6661321
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项目类别:
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资助金额:$21.74万
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财政年份:2002
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负责人:Victoria L Bautch
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依托单位:
Integrating Cell Division and Morphogenesis in Vessels
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批准号:6785380
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项目类别:
-
资助金额:$21.74万
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财政年份:2002
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负责人:Victoria L Bautch
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依托单位:
海外基金