NO通路与动脉粥样硬化

NO(,610081)NO1986,,NONO;ADMA-DDAH;R-1,R54114ANOPathwayandAtherosclerosisSUNJing(DepartmentofPathology,ChengduMedicalCollege,Chengdu610083,China)Abstract:PeoplehaspaidmoreandmoreattentiontoNOsinceitsimportantfunctioninendotheliumwasfoundin1986,andithasbecomeanewhotresearchpointofthepathogenesisofatherosclerosis.ThispaperbrieflyreviewstherelationshipbetweenNOpathwayandatherosclerosis.Keywords:NOpathway;ADMA-DDAHsystem;atherosclerosis2006-12-142007-03-13(1979-),,,,,1982Furchogott,(DERF)[1],1986Lgnar2roEDRF(NO)[2],NO,NO1,,,,,,,[1,3],ross,2L-arg/NOL-arg/NONOL-arg,L-(L-OH-Arg)NONOSNOS:cNOSiNOSnNOS[3]cNOS,NADPH,,NOSiNOS,,,,NOS,NOS,NOSNOcNOSnNOS,cNOSnNOS,iNOS,cNOSnNOSiNOSNO,,iNOSNO,,JOURNALOFCHENGDUMEDICALCOLLEGE200721NO,NO[3]NONONO,,NOLDLNONONO3ADMA-DDAH,()DDAHADMA,NOSNO[4],L-arginine-NOS-NOADMA-DDAH[5],NOS(ADMA)L-,L-,,L-argi2nineeNOS[7,8]ADMA,NO,NO,ADMADDAHL-[7,8]90%ADMADDAHDDAHADMA[4,7,8]DDAH,[6,8]DDAH:DDAHDDAHDDAHNOS,DDAHNOSDDAH4NOADMA-DDAH,,(reactiveoxygenspecies,ROS),[10,11],,[12],NO[13],PRMTDDAHNO-(ADMA)NO[14],ADMADDAH(reactivecysteineresidueCys-249)[14],,,DDAHADMA,NO,ADMAADMADDAH,ADMA[15]ADMAL-NOS,NO,ADMANOS,-1(monocytechemotacticprotein-1,MCP-1)[16],:ADMA,,ADMANOS,,Fe-S,NOLOLOO,27JOURNALOFCHENGDUMEDICALCOLLEGE2007215NOADMA-DDAHADMANOS,-1(monocytechemotacticprotein-1,MCP-1)[17],:ADMANO,-KB(NF-KB),[18]:(M-CSF)-1(MCP-1)/-KB,6NOADMA-DDAH,,NOScNOSBH4[19],,,,NADHNADPH[20],,,,NONOS,,(ET),ADMA,NO,NO/ET,,7NOADMA-DDAH,,NOSBH4,NO,,DDAH,ADMA[21],,Ca2+,eNOSNO;iNOSNO,GSH-PX(advancedglycosy2latonendproduction,AGE),NO[22]C[22]NO8NOADMA-DDAH,NOSL-Arginine/ADMA,ADMA(TC)(LDL)[23]ox-LDLNONO,,ox-LDL,NO,NO,,ox-LDLeNOS,NO[24-26]:DDAH,ADMAox-LDL-kB,TNF-a,TNF-aADMAox-LDLPRMTs,ADMAox-LDL,NO,NOSADMA,ox-LDLNOS,NO,NOSBH4,NOLDL[25,26],LDLNOSLDLNO37J.CDMC2007,2(1)1NO9,NOADMA-DDAH,,ADMANO?NOADMA-DDAH:[1]Landmesser,Hornig,Burkhard,etal.Helmut.EndothelialFunc2tion:aCriticalDeterminantinAtherosclerosis?[J].Circulation,2004,109(21):Supplement::27-33.[2]PalmerRMJ,FerrigeAG,MoncadaS.NitricOxideReleaseAc2countsfortheBiologicalActivityofEndothelial-derivedRelaxingFactor[J].Nature,1987,327:524-526.[3]Rabelink,TonJ,Luscher,etal.EndothelialNitricOxideSynthase:HostDefenseEnzymeoftheEndothelium?[J].Arteriosclerosis,Thrombosis&VascularBiology,2006,26(2):267-271.[4]Zoccali,Carmine.AsymmetricDimethylarginine(ADMA):aCar2diovascularandRenalRiskFactorontheMove[J].JournalofHy2pertension,2006,24(4):611-619.[5]DayoubHayan,AchanVinod,Adimoolam,etal.AsymmetricDimethy2larginine,DerangementsoftheEndothelialNitricOxideSynthasePathwayandCardiovascularDiseases[R].SeminarsinThrombosis&Hemosta2sis,2000,26(5):539-545.[6]Eiper,JamesM.TheDDAH-ADMA-NOSPathway[J].Thera2peuticDrugMonitoring,2005,27(6):744-746.[7]CookeJP.DoesADMACauseEndothelialDysfunction?[J].Arte2riosclerThrombVascBiol,2000,20:2032-2037.[8]CookeJP,JohnP.AsymmetricalDimethylarginine:TheUberMark2er?[J].Circulation,2004,109(15):1813-1818.[9]LuTM,DingYA,CharngMJ,etal.AsymmetricalDimethylargi2nine:aNovelRiskFactorforCoronaryArteryDisease[J].ClinCardiol,2003,26:458-464.[10]FreemaBA,CrapoJD.FreeRadicalsandTissueInjury[J].Biolo2gyofDisease,1982,47:412-426.[11]KenYL,AkiraI,TomokoA,etal.ImpairedNitricOxideSynthasePathwayIndiabetesMellitus[J].Circulation,2002,106:987-992.[12]CifuentesMEugenia,Pagano,PatrickJ.TargetingReactiveOxygenSpeciesinHypertension[J].CurrentOpinioninNephrology&Hy2pertension,2006,15(2):179-186.[13]Uzik,TomaszJ,SadowskiJerzy,etal.CoronaryArterySuperox2ideProductionandNoxIsoformExpressioninHumanCoronaryArteryDisease[J].Arteriosclerosis,Thrombosis&VascularBiology,2006,26(2):333-339.[14]OsanaiTomohiro,Saitoh,Masayuki,etal.KenEffectofShearStressonAsymmetricDimethylarginineReleaseFromVascularEn2dothelialCells[J].Hypertension,2003,42(5):985-990.[15]YinQing-feng,XiongYan.PravastatinRestoresDDAHActivityandEndothelium-DependentRelaxationofRatAortaAfterExposuretoGlycatedProtein[J].JournalofCardiovascularPharmacology,2005,45(6):525-532.[16]MatataBM,Galinanes.PeroxynitriteIsanEssentialComponentofCytokinesProductionMechanisminHumanMonocytesthroughModu2lationofNuclearFactor-kappaBDNABindingActivity[J].Bi2olchem,2002,277:2330-2335.[17]Cooke,JohnP.AsymmetricalDimethylarginine:TheUberMarker?[J].Circulation,2004,109(15):1813-1818.[18]MinoT,KitakazeM,sanadaS,etal.IncreasedExpressionofP-selectinonPlateletsIsaRiskFactorforSilentCerebralInfarctioninPatientswithAtrialFibrillation[J].Circulation,1998,98:1721-1727.[19],,.B(NuclearFactorB,NF-B):[J].,1999,5(4):289-295.[20],,,.-1[J].,1999,14(6):352-354.[21]StithlingerMC,AbbasiF,Chu3W,etal.RelationshipbetweenInsulinResistanceandallEndogenousNitricOxideSynthaseInhibitor[J].JAMA,2002,287:1420-1426.[22]HigginbottomA,TakahashiY,BollingL,etal.StructuralRe2quirementsfortheInhibitoryActionoftheCD9LargeExtracellularDomaininSperm/oocyteBindingandFusion[J].BiochemBiophysResCommun,2003,311(1):208-214.[23]RippinJD,PatelA,BelyaevND,etal.NitricOxideSynthaseGeneKolymorphismandDiabeticNephropathy[J].Diabetologia,2003,46(12):1707-1708.[24]Landmesserurf,hornig,burkhard,etal.EndothelialDysfunct