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ID:19848376
大小:15.73 MB
页数:21页
时间:2018-10-07
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1、FightingRestenosis:Targetingc-CblNanpingWangInstituteofCardiovascularSciencePekingUniversity1Coronaryarterydisease:asignificanthealththreatafflictingmillionsofindividualsworldwide.Despitethedevelopmentofavarietyoftechnologiesandcatheterbasedinterventions,post-procedurerestenosisisstillasignifican
2、tconcern.Genetherapyhasemergedasapromisingapproachaimedatmodifyingcellularprocessesthatgiverisetorestenosis.Restenosis2GeneTherapy-PreclinicalStudyRissanenandYla-Herttuala.MolTher.2007;15:1233-473c-CblCellularhomologueofretroviraloncogenicproteinv-CblwhichinducesCasitasB-lineagelymphoma.Anadaptorp
3、roteinandanE3ubiquitinligase.Tyrosinephosphorylatedinresponsetovariousincludingintegrinsandactivationofreceptortyrosinekinases(PDGFRandFGFR).4AimoftheStudyTodeterminethepathophysiologicalroleofc-CblinvascularinjuryresponseinSMCsinvitroandballoon-injuredarteriesinvivo.5c-CblTyrosinePhosphorylationI
4、sIncreasedinInjuredArteries6PDGFIncreasedc-CblTyrosinePhosphorylationinSMCs7AHierarchicalSignalingCascadefromc-CbltoPI3K/akt/mTORinSMCs8Ablationofc-CblTyrosinePhosphorylation:ATooltoFightRestenosis?9ConditionalExpressionofc-CblMutantinSMCs10c-Cbl-mSuppressedSMCProliferationandMigration11c-Cbl-mRes
5、trictedG1/SProgressioninSMCs12c-Cbl-mInhibitedPI3K/Akt/mTORActivationinSMCs13ConstitutiveActivationofPI3KorAktAttenuatedthec-Cbl-mEffects1415c-Cbl-mIncreasedUbiquitinationofPDGFandFGFReceptors16Adenovirus-mediatedGeneTransferofc-Cbl-mInhibitsAkt/mTORActivationinvivo17c-Cbl-mInhibitsSMCProliferatio
6、nandMigrationinvivo18c-Cbl-mInhibitsIntimalHyperplasiainBalloon-injuredArteries19Proposedroleofc-CblinvascularRemodeling20AcknowledgmentNationalScienceFoundationofChinaMajorGrantforDiabetesResearch,MOSTZhihuiTang,YingWang,YanboFan21
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