Proteomic Analysis of Aortae from Human Lipoprotein(a) Transgenic Mice Shows an Early Metabolic Response Independent of Atherosclerosis 英文参考文献.docVIP

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Proteomic Analysis of Aortae from Human Lipoprotein(a) Transgenic Mice Shows an Early Metabolic Response Independent of Atherosclerosis 英文参考文献.doc

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Proteomic Analysis of Aortae from Human Lipoprotein(a) Transgenic Mice Shows an Early Metabolic Response Independent of Atherosclerosis 英文参考文献

ProteomicAnalysisofAortaefromHumanLipoprotein(a) TransgenicMiceShowsanEarlyMetabolicResponse IndependentofAtherosclerosis EuanJ.Rodger1,RachelJ.Suetani1,GregoryT.Jones2,TorstenKleffmann3,AlanCarne1,MichaelLegge1, SallyP.A.McCormick1* 1DepartmentofBiochemistry,UniversityofOtago,Dunedin,NewZealand,2DepartmentofSurgicalSciences,UniversityofOtago,Dunedin,NewZealand,3Centrefor ProteinResearch,UniversityofOtago,Dunedin,NewZealand Abstract Background:Elevatedlowdensitylipoprotein(LDL)andlipoprotein(a)areindependentriskfactorsforthedevelopmentof atherosclerosis. Using a proteomic approach we aimed to determine early changes in arterial protein expression in transgenicmicecontainingbothhumanLDLandlipoprotein(a)incirculation. MethodsandResults:Plasmalipidanalysesshowedthelipoprotein(a)transgenicmicehadsignificantlyhigherlipidlevels than wildtype, including a much increased LDL and high density lipoprotein (HDL) cholesterol. Analysis of aortae from lipoprotein(a) mice showed lipoprotein(a) accumulation but no lipid accumulation or foam cells, leaving the arteries essentiallyatherosclerosisfree.Usingtwo-dimensionalgelelectrophoresisandmassspectrometry,weidentified34arterial proteinswithsignificantlyalteredabundance(P,0.05)inlipoprotein(a)transgenicmicecomparedtowildtypeincluding17 thatshoweda$2folddifference.Someproteinsofinterestshowedasimilarlyalteredabundanceatthetranscriptlevel. Thesechangescollectivelyindicatedaninitialmetabolicresponsethatincludedadownregulationinenergy,redoxand lipidmetabolismproteinsandchangesinstructuralproteinsatastagewhenatherosclerosishadnotyetdeveloped. Conclusions:OurstudyshowsthathumanLDLandlipoprotein(a)promotechangesintheexpressionofauniquesetof arterialproteinswhichmaybeearlyindicatorsofthemetabolicdisturbancesprecedingatherosclerosis. Citation:RodgerEJ,SuetaniRJ,JonesGT,KleffmannT,CarneA,etal.(2012)ProteomicAnalysisofAortaefromHumanLipoprotein(a)TransgenicMiceShowsan EarlyMetabolicResponseIndependentofAtherosclerosis.PLoSONE7(1):e30383.doi: