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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Adenosine stimulates angiogenesis by up‐regulating production of thrombospondin‐1 by macrophages
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Adenosine stimulates angiogenesis by up‐regulating production of thrombospondin‐1 by macrophages

机译:腺苷通过上调巨噬细胞对血小板反应蛋白-1的产生来刺激血管生成

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IncreaseofbloodcapillarydensityattheinterfacebetweennormalandischemictissueafteracuteMIreducesinfarctsizeandimprovescardiacfunction.CardiacinjurytriggerstheproductionofthematricellularcomponentTSP‐1,butitsroleinangiogenesisisnotclear,asbothanti‐andproangiogenicpropertieshavebeenreported.ItisunknownwhetherTSP‐1ismodulatedbyotherfactorsreleasedduringcardiacinjury.Amongthese,Adoisawell‐knownpromoterofangiogenesis.ThisstudydeterminedwhetherAdomodulatesTSP‐1expressionandtheimplicationonangiogenesis.AdodosedependentlyincreasedtheproductionofTSP‐1byhumanmacrophages.WiththeuseofagonistsandantagonistsofAdoRs,coupledtoRNAinterference,weobservedthatthiseffectismediatedviaA2ARandA2BR.TheAdoeffectwasreproducedbycholeratoxin(Gsproteinactivator)andforskolin(adenylatecyclaseactivator)andblockedbythePKAinhibitorH89.ConditionedmediumfromAdo‐treatedmacrophagesstimulatedmicrovesseloutgrowthfromaorticringexplantsby400%,andinducedvesselformationinmatrigelplugs.Microvesseloutgrowthandvesselformationwereblockedcompletelybyadditionofanti‐TSP‐1antibodiestoconditionedmedium.ChronicadministrationofAdotoratsafterMImaintainedlong‐termexpressionofTSP‐1intheinfarctborderzone,andthiswasassociatedwithenhancedborder‐zonevascularization.Adoup‐regulatesTSP‐1productionbymacrophages,resultinginstimulationofangiogenesis.ThemechanisminvolvesA2ARandA2BRandismediatedthroughthecAMP/PKApathway.ThisinformationmaybeimportantwhendesigningAdo‐basedtherapiesofangiogenesis...
机译:IncreaseofbloodcapillarydensityattheinterfacebetweennormalandischemictissueafteracuteMIreducesinfarctsizeandimprovescardiacfunction.CardiacinjurytriggerstheproductionofthematricellularcomponentTSP-1,butitsroleinangiogenesisisnotclear,asbothanti-andproangiogenicpropertieshavebeenreported.ItisunknownwhetherTSP-1ismodulatedbyotherfactorsreleasedduringcardiacinjury.Amongthese,Adoisawell-knownpromoterofangiogenesis.ThisstudydeterminedwhetherAdomodulatesTSP-1expressionandtheimplicationonangiogenesis.AdodosedependentlyincreasedtheproductionofTSP-1byhumanmacrophages.WiththeuseofagonistsandantagonistsofAdoRs,coupledtoRNAinterference,weobservedthatthiseffectismediatedviaA2ARandA2BR.TheAdoeffectwasreproducedbycholeratoxin(Gsproteinactivator)andforskolin(adenylatecyclaseactivator)andblockedbythePKAinhibitorH89.ConditionedmediumfromAdo-treatedmacrophagesstimulatedmicrovesseloutgrowthfromaorticringexplantsby400% ,并在基质栓塞上诱发血管形成。微血管外生长手血管形成被阻塞edcompletelybyadditionofanti-TSP-1antibodiestoconditionedmedium.ChronicadministrationofAdotoratsafterMImaintainedlong-termexpressionofTSP-1intheinfarctborderzone,andthiswasassociatedwithenhancedborder-zonevascularization.Adoup-regulatesTSP-1productionbymacrophages,resultinginstimulationofangiogenesis.ThemechanisminvolvesA2ARandA2BRandismediatedthroughthecAMP / PKApathway.ThisinformationmaybeimportantwhendesigningAdo-basedtherapiesofangiogenesis ...

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