Estradiol Stimulates Vasodilatory and Metabolic Pathways in Cultured Human Endothelial Cells 英文参考文献.docVIP

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Estradiol Stimulates Vasodilatory and Metabolic Pathways in Cultured Human Endothelial Cells 英文参考文献.doc

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Estradiol Stimulates Vasodilatory and Metabolic Pathways in Cultured Human Endothelial Cells 英文参考文献

EstradiolStimulatesVasodilatoryandMetabolic PathwaysinCulturedHumanEndothelialCells AguaSobrino1,ManuelMata2,Andre′sLaguna-Fernandez1,SusanaNovella1,3,PilarJ.Oviedo1 ,Miguel AngelGarc?′a-Pe′rez1,JuanJ.Tar?′n4,AntonioCano5,CarlosHermenegildo1,3* 1ResearchFoundation,HospitalCl?′nicoUniversitario,UniversityofValencia,Valencia,Spain,2ResearchFoundation,HospitalGeneralUniversitario,UniversityofValencia, Valencia,Spain,3DepartmentofPhysiology,UniversityofValencia,Valencia,Spain,4DepartmentofFunctionalBiologyandPhysicalAnthropology,UniversityofValencia, Valencia,Spain,5DepartmentofPediatrics,ObstetricsandGynecology,UniversityofValencia,Valencia,Spain Abstract Vasculareffectsofestradiolarebeinginvestigatedbecausetherearecontroversiesamongclinicalandexperimentalstudies. DNAmicroarrayswereusedtoinvestigateglobalgeneexpressionpatternsinculturedhumanumbilicalveinendothelial cells (HUVEC) exposed to 1nmol/L estradiol for 24hours. When compared to control, 187 genes were identified as differentially expressed with 1.9-fold change threshold. Supervised principal component analysis and hierarchical cluster analysisrevealedthedifferencesbetweencontrolandestradiol-treatedsamples.Physiologicalconcentrationsofestradiol aresufficienttoelicitsignificantchangesinHUVECgeneexpression.Notchsignaling,actincytoskeletonsignaling,pentose phosphatepathway, axonalguidancesignaling andintegrin signaling werethetop-five canonicalpathways significantly regulated by estrogen. A total of 26 regulatory networks were identified as estrogen responsive. Microarray data were confirmed by quantitative RT-PCR in cardiovascular meaning genes; cyclooxigenase (COX)1, dimethylarginine dimethylaminohydrolase(DDAH)2,phospholipaseA2groupIV(PLA2G4)B,and7-dehydrocholesterolreductasewereup- regulatedbyestradiolinadose-dependentandestrogenreceptor-dependentway,whereasCOX2,DDAH1andPLA2G4A remainedunaltered.Moreover,estradiol-induced COX1geneexpressionresulted inincreased COX1proteincontentand enhanced prostacy