PGC-1α Inhibits Oleic Acid Induced Proliferation and Migration of Rat Vascular Smooth Muscle Cells 英文参考文献.docVIP

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PGC-1α Inhibits Oleic Acid Induced Proliferation and Migration of Rat Vascular Smooth Muscle Cells 英文参考文献.doc

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PGC-1α Inhibits Oleic Acid Induced Proliferation and Migration of Rat Vascular Smooth Muscle Cells 英文参考文献

PGC-1aInhibitsOleicAcidInducedProliferationand MigrationofRatVascularSmoothMuscleCells YanZhang1.,ChangLiu1.,LingyunZhu1,XiaohongJiang1,XiChen1,XiaoqiangQi1,XiangyingLiang1,SoniaJin2,PeixiangZhang1,QingguoLi3, DongjinWang3,XiaofengLiu1,KeZeng1,JunfengZhang1*,YangXiang1*,Chen-YuZhang1* 1Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, People’s RepublicofChina,2MassachusettsInstituteofTechnology,Cambridge,Massachusetts,UnitedStatesofAmerica,3DepartmentofThoracicSurgery, TheAffiliatedDrumTowerHospitalofNanjingUniversityMedicalSchool,Nanjing,People’sRepublicofChina Background. Oleic acid (OA) stimulates vascular smooth muscle cell (VSMC) proliferation and migration. The precise mechanismisstillunclear.Wesoughttoinvestigatetheeffectsofperoxisomeproliferator-activatedreceptorgamma(PPARc) coactivator-1alpha(PGC-1a)onOA-inducedVSMCproliferationandmigration.PrincipalFindings.Oleateandpalmitate,the mostabundantmonounsaturatedfattyacidandsaturatedfattyacidinplasma,respectively,differentlyaffectthemRNAand proteinlevelsofPGC-1ainVSMCs.OAtreatmentresultedinareductionofPGC-1aexpression,whichmayberesponsiblefor theincreaseinVSMCproliferationandmigrationcausedbythisfattyacid.Infact,overexpressionofPGC-1apreventedOA- induced VSMC proliferation and migration while suppression of PGC-1a by siRNA enhanced the effects of OA. In contrast, palmiticacid(PA)treatmentledtooppositeeffects.ThissaturatedfattyacidinducedPGC-1aexpressionandpreventedOA- inducedVSMCproliferationandmigration.MechanisticstudydemonstratedthattheeffectsofPGC-1aonVSMCproliferation andmigrationresultfromitscapacitytopreventERKphosphorylation.Conclusions.OAandPAregulatePGC-1aexpressionin VSMCsdifferentially.OAstimulatesVSMCproliferationandmigrationviasuppressionofPGC-1aexpressionwhilePAreverses the effects of OA by inducing PGC-1a expression. Upregulation of PGC-1a in VSMCs provides a potential novel strategy in preventingatherosclerosis.