C3 Localization of cardiac transforming growth factor beta-1 and its receptor in human heart failure

POSTERS:Cell Biologyand GrowthFactors

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c Preeence of Cardiacp53in HumanHeartFaiiure. H Song,S Ren, F Xia, R Zhang,CM Wei*. Univ.of MaryiandSchooiof Medicine,Baltimore,MD. p53 is a tumorsuppressorgenewhichis responsibleforcertainstressinducedapoptosisand ceiicyciearrest. The expressionof p53 is associatedwiththe developmentof mronaryartery restenosisafterangiopiastyin humansand with ischemia-reperfimsion inducedmyocardiai apoptosisin rat. However,the statusof p53 in humancardiomyocytes andfibroblastein congestiveheartfeiiure(CHF) remains controvereiai.The presentstudywas designedto investigatethe p53 in humanventricular myocardiumin normalsubjectsand in patientswith CHF. Fivenormaisubjectsandfiveend-stage failinghumanventricularmyocardiumtissuewere obtainedfromcardiactransplantation.The expressionof p53 proteinin cardiactissueswas determinedby immunohistochemical staining. p53 proteinwas notdetectablein norrnaihuman ventricularcardiomyocytes.in contrast,the staining densitiesof p53 weresignificantlyincreasedin nucleareofventricularcerdiomyocytes in patients withsevereCHF. p53 was notexpressedin cardiac fibrobiastebothfromnonnaiand CHF patients. The expressionof p53 in CHF cardiomyocytes butnotin norrnaisubjectssuggestthat p53 may playan importantroleinthe proceesesof CHF through mechanismsinvoivingmyocardialapoptosis. KeyWords: apoptosis,p53, rmrgeetiveheartfailure

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GLUCOSE INCREASES PROLIFERATION OF VASCULAR SMOOTH MUSCLE CELLS INDUCED BY LDL K. Lottermoser,B. Weisser, S. Seewald, A. Sachinidis,and H. Vetter. MediziniechePoliklinik, University of &mn, Germany,

LOCALIZATION OF CARDiACTRANSFORMING GROWTHFACTORBETA-1ANDiTSRECEPTORiN HUMANHEARTFAiLURE.S Ren,H Song,CM Wei*. Univ.of MaryiandSchoolof Medicine,Baltimore,MD. Transforminggrowthfactor-beta(TGF+3)is a growthreguiatingproteinthat has been shownto enhance coiiagenproductionin culturedceiis. The present studywas designedto determinethe TGF-~1 and its receptorin humanventricularmyocardiumin norrnai subjects(n=5) and in patientswithend-stage congestiveheartfaiiure(CHF, n=5)whichwere obtainedfromcardiactranspiantation. TGF-~1 and TGF-j3typei receptor(TGF13RI)weredeterminedby immunohistochemicai staining. BothTGF-~1 and TGF~Rl were steinedin normaihumanventricular tissueand significantly increasedin CHF patients.Both TGF-~1 andTGF~Rl were iocaiizedin cytoplasmand peri-nuciearregionof cardiomyocytes.The staining scoresand ‘Apositivestainingarea (“A+)are demonstrateinthe tabie. TGF-01 Scores scores %(+) %(+) Normal 1.16 1 57% 72% CHF 2.74 2.32 Thesedate suggestthatTGF-~1 andTGF~Rl are presentin norrnaihumanventricuiartissueand increasedin CHF ventricularcardiomyocytes.These studiesdemonstratedthatTGF-pl may piayan importantpathophysioiogic rolein humanheartfailure.

Vascularhypertrophy mightbe oneof the slow pressormechanismsinvolvedin bloodpressure regulationand it has been shown that lipids inducegrowthof vascularsmmth musclecells (VSMC)in vitro.Bothchangesin lipidmetabolism and increasedserumglucoselevelshave been shownin the matabolicsydromeand mighthave an effecton vascularbiology.Inthe presentstudy, the influenceof increasedglucoseconcentrations on VSMC-proliferationwas investigated.VSMC were culturedfrom rat aortaand DNAsynthesis was measuredby incorporationof sH-thymidine during 24 hrs. LDL was isolated by density gradientultracentrifugation. LDL (50pg/ml,n=6) increasedthymidineincorporation(cpm/pgcell protein)from 180&?4(control,glucoseconcentration50mg/dl)to 345*5 (LDL),pcO.05.Glucose also increasedDNA synthesisto 320 ~ 55 (100 mg/dl)and to 410 ~ 64 (150 mg/dl).In addition, LDL-inducedproliferationof vascular smooth musclecells was potentiatedby higherglucose concentrationin the culturemedium(512 ~76 cpm, 100 mg/dl and 615 + 71cpm,150 mg/dl), Thus, increasedglucoselevels mightincrease DNA synthesisin VSMC and mighttherebyinfluencebothatherogeneais andpossiblylong-term bloodpressurecontrol. Keywords: Glucose,LDL,proliferation

KeyWords:Transforminggrowthfactor-beta,congestive heartfeiiure,cytokine,cardiomyocyte

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