Blockade of VEGFR2 and Not VEGFR1 Can Limit Diet-Induced Fat Tissue Expansion Role of Local versus Bone Marrow-Derived Endothelial Cells 英文参考文献.docVIP

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Blockade of VEGFR2 and Not VEGFR1 Can Limit Diet-Induced Fat Tissue Expansion Role of Local versus Bone Marrow-Derived Endothelial Cells 英文参考文献.doc

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Blockade of VEGFR2 and Not VEGFR1 Can Limit Diet-Induced Fat Tissue Expansion Role of Local versus Bone Marrow-Derived Endothelial Cells 英文参考文献

BlockadeofVEGFR2andNotVEGFR1CanLimitDiet- InducedFatTissueExpansion:RoleofLocalversusBone Marrow-DerivedEndothelialCells JoshuaTam1,2.,DanG.Duda1.,JeanY.Perentes1,3.,RehanS.Quadri1,DaiFukumura1*,RakeshK.Jain1* 1EdwinL.SteeleLaboratory,DepartmentofRadiationOncology,MassachusettsGeneralHospitalandHarvardMedicalSchool,Boston,Massachusetts,UnitedStatesof America,2Harvard-MassachusettsInstituteofTechnologyDivisionofHealthSciencesandTechnology,MassachusettsInstituteofTechnology,Cambridge,Massachusetts, UnitedStatesofAmerica,3DivisionofThoracicandVascularSurgery,CentreHospitalierUniversitaireVaudois(CHUV),Lausanne,Switzerland Abstract Background:Weinvestigatedifnewvesselformationinfatinvolvesthecontributionoflocaltissue-derivedendothelialcells (i.e.,angiogenesis)orbonemarrow-derivedcells(BMDCs,i.e.vasculogenesis)andifantiangiogenictreatmentbyblockade ofvascularendothelialgrowthfactor(VEGF)receptorscanpreventdiet-inducedobesity(DIO). Methodology/Principal Findings: We performed restorative bone marrow transplantation into wild-type mice using transgenic mice expressing green fluorescent protein (GFP) constitutively (driven by b-actin promoter) or selectively in endothelial cells (under Tie2 promoter activation) as donors. The presence of donor BMDCs in recipient mice was investigatedinfattissuevesselsafterDIOusinginvivoandexvivofluorescencemicroscopy.Weinvestigatedtherolesof VEGFreceptors1and2(VEGFR1/VEGFR2)byinducingDIOinmiceandtreatingthemwithblockingmonoclonalantibodies. Wefoundonlymarginal(lessthan1%)incorporationofBMDCsinfatvesselsduringDIO.Whenangiogenesiswasinhibited byblockingVEGFR2inmicewithDIO,treatedmicehadsignificantlylowerbodyweightsthancontrolanimals.Incontrast, blockingVEGFR1hadnodiscernableeffectontheweightgainduringDIO. Conclusions/Significance:FormationofnewvesselsinfattissuesduringDIOislargelyduetoangiogenesisratherthande novovasculogenesis.AntiangiogenictreatmentbyblockadeofVEGFR2butnotVEGFR1maylimitadiposetissueexpansion. Citation:TamJ,DudaDG,Perentes