Differential Regulation of PDE5 Expression in Left and Right Ventricles of Feline Hypertrophy Models 英文参考文献.docVIP

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Differential Regulation of PDE5 Expression in Left and Right Ventricles of Feline Hypertrophy Models 英文参考文献.doc

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Differential Regulation of PDE5 Expression in Left and Right Ventricles of Feline Hypertrophy Models 英文参考文献

DifferentialRegulationofPDE5ExpressioninLeftand RightVentriclesofFelineHypertrophyModels XiaoyinShan,KennethB.Margulies* CardiovascularInstitute,UniversityofPennsylvaniaSchoolofMedicine,Philadelphia,Pennsylvania,UnitedStatesofAmerica Abstract Background:Thoughlongknowntoaffectsmoothmusclebiology,recentstudiesindicatethatphosphodiesterase5(PDE5) is also expressed in myocardium. Recognizing that the regulation of PDE5 in hypertrophy is not well understood, we assessedtheresponseofPDE5expressionandthelevelofcGMP-dependentkinaseI(cGKI)intheleftandrightventriclesof felinehypertrophymodels. Methodology/PrincipalFindings:UsingacDNAlibraryoffelineaorticsmoothmusclecells,weidentifiedandclonedPDE5 cDNAforthefirsttimeinthisspecies.Thesequenceshares98%identitywithitshumanorthologueattheaminoacidlevel. E.coliexpressionoftheclonedalleleallowedselectionofantibodieswithappropriatespecificity,facilitatingtheanalysisof PDE5expressioninfelinemodelscreatedbyselectiveproximalaortic(Ao)orpulmonaryartery(PA)bandingthatresultedin hypertrophy of the left ventricle (LV) and right ventricle (RV), respectively. We demonstrated that PDE5 expression responded differentially with adecreased expression in the LV and anincreased expression in theRV in the Ao-banded model. Similarly, in the PA-banded model, LV showed reduced expression while the RV expression was unaltered. In addition,theexpressionofcGKIwassignificantlydecreasedintheRVofAo-bandedgroup,correlatinginverselywiththe increaseinPDE5expression. Conclusions/Significance:ThedifferentialregulationofPDE5andcGKIexpressionsuggeststhatthemechanismsinvolved inhypertrophycouldbedifferentinRVvs.LV.ReciprocalPDE5andcGKIexpressionintheRVofAo-bandedmodelsuggests functionalsignificanceforPDE5up-regulation. Citation: Shan X, Margulies KB (2011) Differential Regulation of PDE5 Expression in Left and Right Ventricles of Feline Hypertrophy Models. PLoS ONE 6(5): e19922.doi:10.1371/journal.pone.0019922 Editor:MartinR.J.Kolb,McMasterUniversity,Canada Recei