肾上腺髓质素对血管钙化的抑制作用PPT课件.ppt

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1、AdrenomedullininhibitsvascularcalcificationDepartmentofPhysiologyandPathophysiology,PekingUniversityHealthScienceCenterKeyLaboratoryoftheMinistryofEducationonMolecularCardiologyYong-FenQiVascularcalcificationHypertensionDiabetesMellitusHyperlipemiaRenalFailureAgingMediaIntimaVas

2、cularcalcificationisbelievedtobeanimportantriskfactorofcardiovasculardiseasesAtherosclerosisVasoactivepeptides:Adrenomedullin?Adrenomedullin(ADM)isapeptidecapableofinducingapotentandlonglastinghypotensiveeffectADMismainlysynthesizedandsecretedfromvascularendothelialandsmoothmuscl

3、ecells(VSMC)ADMhasbeenshowntohavevasodilatory,hypotensiveandgrowthregulatingproperties,ExogenousADMorADMgenedeliveryattenuatedhypertensionandprotectedagainstcardiovascularremodeling,butADMgeneknockoutresultedinhigherbloodpressureandcardiovascularabnormalities.EndogenousADMisanimp

4、ortantfactorinregulatingcardiovascularandrenalhomoestasis,andisapotentcardio-reno-protectivefactorreceptorsboundwithADMwereorphanL-1andRDC-1receptorsInaddition,anotherorphanreceptornamedcalcitoninreceptor-likereceptor(CRLR)couldbindwithADMwhenreceptoractivity-modifyingprotein(RAM

5、P)2and/orRAMP3existedoncellularmembranesurfaceFig.1.(A)Calcificationofmulticellularnodules.vonKossastainingforcalcification,showingpositivestainingasblack/brownareaswithinthemain,large,nodularstructure(originalmagnification40×).(B)Formationofmulticellularnodulesinculturephasecont

6、rastmicroscopyshowingratVSMCs(originalmagnification20×).AB45Ca-uptake(103cpm/mgPr)Cacontent(nmol/mgPr)ALPactivity(U/mgPr)Control32.2±5.2046.8±7.2374±11CalcifiedVSMC88.2±10.21**102.2±18.23**624±84**Table:GeneralindexofcalcifiedVSMCs.(n=6,X±S.D.)ALP:alkalinephosphatase.**p<0.01vs.c

7、ontrol.**ADMcontentincalcifiedVSMCADMmRNArelativeamountincalcifiedVSMCCRLRmRNARAMP2mRNARAMP3mRNAβ-actinmRNA446bp416bp371bp291bpCCRLRCRAMP2CRAMP3AlterationsofCRLR,RAMP2，RAMP3mRNAincalcifiedVSMCsmRNAexpressionweredeterminedbysemi-quantitativeRT-PCRanalysis.CRLR:calcitoninreceptorli

8、kereceptor.RAMP:receptoractivitymodifyin