《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