VWF - Mechanisms of Regulation
VWF - Mechanisms of Regulation
批准号:
9762972
负责人:
SANDRA HABERICHTER
金额:
$42.25万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-08-15 至 2022-06-30
关键词:
AdhesionsAffectAlpha GranuleBiological AssayBloodBlood CirculationBlood Coagulation DisordersBlood PlateletsBlood VesselsCarrier ProteinsCellsClinicalCytoplasmic GranulesDDAVPDefectDesmopressinDiagnosisDisease susceptibilityEndothelial CellsEnzyme-Linked Immunosorbent AssayFactor VIIIFactor VIII-Related AntigenFamily memberGalactoseGlycoproteinsHalf-LifeHemorrhageHemostatic functionImpairmentIndividualInheritedInjuryKnowledgeLectinLinkLongevityMammalian CellMannoseMeasuresMediatingMegakaryocytesMetabolic Clearance RateModelingModificationMusPatientsPlasmaPolysaccharidesPopulation ControlProteinsRegulationReportingSamplingSialic AcidsSiteTimeVariantWeibel-Palade Bodiesbasecohortcommon treatmentdisorder subtypeeffective therapyethnic diversityglycoproteomicsglycosylationimprovedindexingmouse modelmutantnovelrelease factorresponsevon Willebrand Diseasevon Willebrand Factorvon Willebrand factor receptor
中文摘要
项目总结
英文摘要
Project Summary
The regulation of plasma von Willebrand factor (VWF) level is critical for hemostasis, as VWF both mediates
platelet adhesion at sites of vascular injury and serves as carrier protein for coagulation factor VIII. Type 1 von
Willebrand disease (VWD) is the most common VWD subtype with quantitative deficiency of VWF. The
reduced survival of plasma VWF is a novel VWD mechanism, termed type 1C. Type 1C VWD patients have a
significantly decreased VWF half-life (1-3 hrs vs 12-16 hrs), which severely impacts the efficacy of DDAVP
treatment. DDAVP releases VWF from endothelial cell storage granules into plasma and is the most common
treatment in type 1 VWD. Rapid VWF clearance substantially impairs therapy of type 1C patients. Type 1C
patients are identified by increased VWF propeptide (VWFpp) to VWF antigen (VWF:Ag) ratio. Our hypothesis
is that the assay of plasma VWFpp and VWFpp/VWF:Ag can be used to predict the release of VWF and its
clearance rate after DDAVP administration in types 1 and 1C VWD. This could potentially reduce the need for
DDAVP trials in patients or affected family members. The underlying mechanisms causing reduced VWF
survival in patients remain largely undefined. A number of studies have suggested a link between VWF
glycosylation and VWF clearance. The glycan composition of VWF was recently determined using pooled
plasma from healthy donors. However, VWF glycan variation in individual healthy controls and VWD patients
has not been studied. Our hypothesis is that type 1C VWD subjects will have an altered VWF glycosylation
profile compared to healthy controls resulting in increased VWF clearance from plasma. We propose to
systematically define this variation in a large cohort of healthy controls and well-characterized VWF patients
and link alteration of VWF glycosylation with increased clearance from plasma. This project is directed at
improving treatment in type 1 VWD patients as well as enhancing our scientific knowledge of VWF glycan
variability and the link to VWF clearance.
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VWF - Mechanisms of Regulation
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批准号:10191003
-
项目类别:
-
资助金额:$41.66万
-
财政年份:2018
-
负责人:SANDRA HABERICHTER
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依托单位:
VWF - Mechanisms of Regulation
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批准号:9982096
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项目类别:
-
资助金额:$42.16万
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财政年份:2018
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负责人:SANDRA HABERICHTER
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依托单位:
MOLECULAR MECHANISMS OF VWF ALTERATION IN VITRO/VIVO
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批准号:7114031
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项目类别:
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资助金额:$18.55万
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财政年份:2005
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负责人:SANDRA HABERICHTER
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依托单位:
MOLECULAR MECHANISMS OF VWF ALTERATION IN VITRO/VIVO
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批准号:7524662
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项目类别:
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资助金额:$19.11万
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财政年份:--
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负责人:SANDRA HABERICHTER
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依托单位:
Molecular Mechanisms of VWF Alteration in Vitro/Vivo
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批准号:8246609
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项目类别:
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资助金额:$30.05万
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财政年份:--
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负责人:SANDRA HABERICHTER
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依托单位:
MOLECULAR MECHANISMS OF VWF ALTERATION IN VITRO/VIVO
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批准号:7652345
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项目类别:
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资助金额:$18.59万
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财政年份:--
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负责人:SANDRA HABERICHTER
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依托单位:
MOLECULAR MECHANISMS OF VWF ALTERATION IN VITRO/VIVO
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批准号:7885355
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项目类别:
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资助金额:$18.25万
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财政年份:--
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负责人:SANDRA HABERICHTER
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依托单位:
MOLECULAR MECHANISMS OF VWF ALTERATION IN VITRO/VIVO
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批准号:7524667
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项目类别:
-
资助金额:$17.68万
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财政年份:--
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负责人:SANDRA HABERICHTER
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依托单位:
海外基金