《Hepatocyte growth factor improves right ventricular remodeling in pulmonary arterial hypertensive rats via decreasing neurohormonal activation and inhibiting apoptosis.》.pdf
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《Hepatocyte growth factor improves right ventricular remodeling in pulmonary arterial hypertensive rats via decreasing neurohormonal activation and inhibiting apoptosis.》.pdf
1924 ChinMedJ2014,127flo)
Originalarticle
Hepatocytegrowthfactorimprovesrightventri·cu-larrem oa…ehngi●n
pulmonaryarterialhypertensiveratsviadecreasingneurohormonal
activationandinhibitingapoptosis
WangXiaolin,WangYongjin,RongShuling,MaHongbiao,MaQingandZhaoJunqing
Keywor~:hepatocytegrowthfactor,pulmonaryarteryhypertension,apoptosis,ventricularremodeling
Background Hepatocytegrowthfactor(HGF)inhibitsthedevelopmentofpulmonaryarteryhypertension(PAH)by
reducingpulmonaryarterypressureandrightventricle(RV)hypertrophy.However,whetherHGFcanpreventRV
remodelingviainhibitingapoptosisinRV cardiomyocytesanddecreasingneurohormonalactivationremainsunknown.
Methods ThePAHandsubsequentRVremodelinginratswereinducedbysubcutaneousinjectionofmonocrotaline
(MeT).ThePAHratsweretransfectedwithadenoviruscarryingHGF(Ad-HGF)viaintratrachealinstillation.Threeweeks
aftertransfection,thehemodynamicsindexesweremeasured,serumlevelsforangiotoninII(ANGII)andbrainnatriuretic
peptide(BNP)weredeterminedbyELISA.HistologicalanalysiswasusedtoassesstheRVhypertrophyandfibrosis.The
cardiomyocyteapoptosisinRVwasassayedbyTUNELstaining.ThemRNA expressionofBNP,angiotensin—converting
enzyme(ACE),BaxandBc1.2inRVwasdeterminedbyreversetranscriptasepolymerasechainreaction(RT.PCR),the
proteinexpressionoftransforminggrowthfactor(TGF)一3[1andtumornecrosisfactor(TNF)一ainRVwasdeterminedby
Westernblotting.
Results HGFtreatmentsignificantlydecreasedthemeanPAH,RV systolicpressure,serum ANG IIandBNP Ievels.
HGF treatmentalsosignificantly decreased theRV hypertrophy,collagendeposition,andthenumberofapoptotic
cardiomyocytes.Moreover.HGFtreatmemtsignificantlydecreasedtheexpressionofBNP,ACE,Bax,TGF一3[1,andTNF—a,
whileitsignificantlyincreasedtheexpressionofBcl-2.
Conclusions GenetransferOfHGFdecreasesMCT-inducedPAH andimprovesRV remodeling.Thiseffectisme
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