ObjectivesTotestthehypothesesthatbonemorphogeneticprotein(BMP)signalingpathwaycomponentsareexpressedinarterialendothelialcells(ECs)andthatBMPsignalinginfluencesendothelialcell(EC)proliferation.MethodsWeusedcellcultureandRT-PCRtodeterminedmRNAexpressionofBMPreceptors(BMPR)-IA,-IB,andII,Smads1,4,5,6,and7,andinculturedhumancoronaryarteryECsatbaselineandafterstimulationwithBMP2(300ng/mLfor6hr),non-radioactivecellproliferationtoexaminecellproliferation.ResultsProteasomeinhibitionhasbeenpreviouslyshowntoenhanceBMPsignalingbypreventingdegradationofBMPpathwaycomponents.Therefore,identicalexperimentswerealsoperformedinthepresenceoftheproteasomeinhibitorepoxomicin.ECsexpressedmRNAforBMPRsIAandII,Smads1,4,5,6,7,andstimulationwitheitherBMP2orepoxomicinresultedinasignificantincreaseinECproliferationmeasuredafter48hoursinadose-dependentfashion.Proliferationwasaccompaniedbyamarkedincreaseinproliferatingcellnuclearantigen(PCNA)expression.Toxicitywasobservedathighdosesofepoxomicin.ConclusionsAllmajorBMPsignalingmoleculesareexpressedbyvascularECsandexpressionoftheseareaffectedbybothBMP2andepoxomicin.BMP2mayregulateECproliferation,suggestingapossibleroleinvascularhomeostasisandvascularpathologiesinvolvingECdenudationorproliferation.
