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Definition Theyarecirculating,bonemarrow-derivedcellsthatarefunctionallyandphenotypicallydistinctfrommatureendothelialcells Theycandifferentiateintoendothelialcellsinvitro,asassessedbyexpressionprofilesandfunctionalcharacteristics Theycancontributetoinvivovasculogenesisand/orvascularhomeostasisEmbryonicEPCAdultEPCOriginanddifferentiationofendothelialprogenitorcellsEPCs’DevelopmentVEGFRandVEGF Receptor VEGFR-1(flt-1) VEGFR-2(flk-1/KDR) VEGFR-3(flt-4) Ligand VEGF、VEGF-B,C,D,EVEGFRandVEGFTiereceptorandligand:受体酪氨酸激酶家族 receptor Tie-1(Tie) Tie-2(Tek) Tie-2ligand:Angiopoietin(Ang,血管生成素) Ang-1:血管内皮化 Ang-2:血管周围细胞和内皮细胞分离Tiereceptorandligand:受体酪氨酸激酶家族 Tie-2缺陷的胚胎不能建立血管结构的完整性 Ang-1缺陷鼠也表现为血管生成缺陷 Ephsfamily Erythropoietinproducinghepatocytereceptor(Eph) Ligand:ephrins(EphA、B) EphB可调节Ang-1和Tie-2的表达CD34+,Flk-1+CD34-selectedculture-dishnon-adherentputativeEPC(CDNAC)changetoamorematureendothelialphenotypeduringdifferentiationwhiletheprogenitorphenotyperemainsstableandthemonocyticphenotypedecreases.CD34-selectedputativeEPCfromculture-dishadherentcells(CDAC)expresslowerlevelsofendothelialandprogenitormarkersthanCDNAC.VEGFR-2/Flk-1+CD34+/VEGFR-2+cellscanbehaveasEPCs. CD133+/CD34+/VEGFR-2+cellsrepresentamoreprimitiveEPC.PutativeEPCstakeupacetylatedlowdensitylipoprotein(Ac-LDL)andbindtheendothelialspecificlectinUEA-1.MobilizationofEPCsMobilizationofEPCsChemotaxis,MigrationandInvasion SDF-1 VEGFEPCswereoriginallythoughttobepresent onlyduringembryonicdevelopment. Evidenceaccumulatingoverseveralyears suggeststhattheycanpersistinadultlife. Thishasgeneratedinterestintheuseof EPCsforneovascularizationofischemicor injuredtissueandfortheclinical assessmentofriskfactorsforvarious diseases. EPCAngiogenesis VasculogenesisAngiogenesis aregulatedprocessinvolvingtheproliferation,andmigrationofendothelialcellsfromadjacentpre-existingbloodvessels.Vasculogenesis aregulatedprocessfollowingdifferentiationofendothelialprogenitorcellsfrommesodermalprecursors/endothelialprogenitorcells(EPCs)Vasculogenesis和An