肾上腺髓质素对血管钙化的抑制作用.ppt

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1、AdrenomedullininhibitsvascularcalcificationVascularcalcificationHypertensionDiabetesMellitusHyperlipemiaRenalFailureAgingMediaIntimaVascularcalcificationisbelievedtobeanimportantriskfactorofcardiovasculardiseasesAtherosclerosisVasoactivepeptides:Adrenomedul

2、lin?Adrenomedullin(ADM)isapeptidecapableofinducingapotentandlonglastinghypotensiveeffectADMismainlysynthesizedandsecretedfromvascularendothelialandsmoothmusclecells(VSMC)ADMhasbeenshowntohavevasodilatory,hypotensiveandgrowthregulatingproperties,ExogenousADMo

3、rADMgenedeliveryattenuatedhypertensionandprotectedagainstcardiovascularremodeling,butADMgeneknockoutresultedinhigherbloodpressureandcardiovascularabnormalities.EndogenousADMisanimportantfactorinregulatingcardiovascularandrenalhomoestasis,andisapotentcardio-r

4、eno-protectivefactorreceptorsboundwithADMwereorphanL-1andRDC-1receptorsInaddition,anotherorphanreceptornamedcalcitoninreceptor-likereceptor(CRLR)couldbindwithADMwhenreceptoractivity-modifyingprotein(RAMP)2and/orRAMP3existedoncellularmembranesurfaceFig.1.(A)C

5、alcificationofmulticellularnodules.vonKossastainingforcalcification,showingpositivestainingasblack/brownareaswithinthemain,large,nodularstructure(originalmagnification40×).(B)FormationofmulticellularnodulesinculturephasecontrastmicroscopyshowingratVSMCs(orig

6、inalmagnification20×).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.control.**ADM

7、contentincalcifiedVSMCADMmRNArelativeamountincalcifiedVSMCCRLRmRNARAMP2mRNARAMP3mRNAβ-actinmRNA446bp416bp371bp291bpCCRLRCRAMP2CRAMP3AlterationsofCRLR,RAMP2，RAMP3mRNAincalcifiedVSMCsmRNAexpressionweredeterminedbysemi-quantitativeRT-PCRanalysis.CRLR:calcitonin

8、receptorlikereceptor.RAMP:receptoractivitymodifyingprotein.**p<0.01,comparedwithcontrol.*********************ExogenousADMinhibitcalcificationofVSMCCellcounts(104cells/ml)3H-TdR(103cpm/mgPr)3H-Le