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Micropartcles in Diseases

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Micropartcles in Diseases

    Micropartcles in Diseases 血栓与止血学2010年第16卷第3

    MicropartclesinDiseases

    Keywords:Microparticle;Thrombotic

    [CLCnumber]R364[Documentcode]

    述评

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    99?

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    (Commentaries)

    BAOChengxin包承鑫

    (InstituteofHematology,ChineseAcademyofMedicalSciences.Tianjin,300020,China)

    disorders;Bleedingdisorders

    C[Article]10096213(2010)0309903

    Microparticles(MPs)aresmallanucleoidphospho

    lipidvesiclesshedfromplatelets,erythrocytes,leukocytes andendothelialcells.MPscontainsamembraneskele. tionandaredefinedbytheirsizeandexpressionontheir surfaceofantigei~specificofparentalcells.Thediameter ofMPsarefrom0.1t0lm.

    TheproductionofMPsisthoughttopredominately occurbyvesiculationorblebbingofthecellmembrane. MPsformationismainlyissuedfromexperimentsper

    formedinvitroonorculturedcells.However,meeha

    nismsinvolvedinMPsformationinvivoremainessential

    lyunknown.ThemechanismofMPsclearancefromthe circulationisnotknown.

    CirculatinglevelsofMPsarethoughttoreflecta balancebetweencellstimulation,proliferation,and death.LevelofMPsreportedfromBerckmansetalin healthysubjects:plateletderivedMPs(PMPs)237

    10./L(116565),granulocytederivedMPs(LMPs)46

    10./L(1694),andendothelialcellMPs(EMPs)64 10/L(16136).PMPsarehighinmenthanin

    women,thenumberandpropertiesofMPsvarieswith age,inadvancingagePMPsbecomemorethrombogenic. ChangesinMPslevelsincirculatingbloodmaybe duetosomepathologicalconditions,forexample,bleed

    ingdiseases,cardiovasculardiseasesorinfectiousdisea

    ses.PMPsarethemostabundant,representingabout 70%90%.

    Activatedplatelatswereconsideredasamajor sourceofPMPs,buttheymayalsobegeneratedby megakaryoeytes,becausethelatterexpressCD42b, ph0sphatidylserine,andCD41inculture.PMPsalsoex

    pressseveralmajorplateletmembranesurfaceproteins includingGPIb,GPIIb,GPma,Pselectin,aswell

    otherplateletproteins(thrombospondinandCXCLche

    mokines).EMPspossessantigensconstitutivelyex

    pressedbymatureendothelialcells(CD144,CD146,CD 105,CD3I,CD34,CD54,CD51,CD62E,CD106) LMPsexpressnumeroussurfaceproteinsincludingCD 31,CD62E,CD144,CD146,aswellCD66b,HLA

    1,FcyR?,complementregulators.

    ProcoagulantpropertiesofcirculatingMPshavelong beenrecognized.withmostevidencepointingtoaTF

dependentmechanism.thePMPsurfacehasapproxi

    mately50to.100foldmoreprocoagulantactivitythan thesurfaceofactivatedplatelets.TFpositiveMPsorigi

    natefrommonocytes.andPMPscanalsobeTFpositive.

    theTFcantransferfrommonoeytesandpossiblypoly

    moorphonuclearleukocytestoplatelets.PMPscarryfac

    tor?bindingsite,GPIb,GP?b/HIa,andvWFon

    theirsurface.EMPshasTFactivity,andalsostimulate plateletaggregationviaVWF.

    RecentlyithasbeenfoundthatMPscantransfer mRNA.MPsoriginatedfromtumorcellscantransfer mRNAtotargetcells,forexcept,theembryonicstem cells?derivedMPscantransfermRNAofpluripotenttran-? seriptionfactortohaematopoietieprogenitorcells.mRNA transferhasalsobeenfoundinangiogenesis,radiation

    injuredlung.Theirimplicationinpathologiesiscurrently beinginvestigated

    IncreasednumbersofMPsarefoundinvariousdis

    easestates,includingcardiovasculardisease,peripheral arterydisease,venousthromboembolism,antiphospholip

    idantibodiessyndrome,andthromboticthrombocytope

    nicpurpura.

    Elevatedareassociatedwithanriskofthrombosis. Endothelialactivationandvascularinflammationare commonpathwaysinthevascularcomplicationofdiabe

    tes,hypertension,coronaryarterysyndromes,andcere- brovasculardisease.Inthevasculardiseases,elevated levelsandfunctionalcapacityofMPsareariskfactorfor arterialdisease.LevelsofbothPMPsandEMPsaresig. nificantlyinereasedinpatientswitharterialdisease.

    Thereareseveralclinicalconditionsassociatedwith elevatedMPs.andmostarealsoassociatedwithanin. creasedriskofthrombosis.

    ElevatedlevelsandfunctionalcapacityofMPswere foundindiabetes.PMPscorrelatewithplateletactivation andEMPsnumberscloselyassociatewitheoronap/ plaques.MonocytederivedLMPsarealsoincreased.

    andcorrelatewithPMPs.annexinVpositionMPscorre

    latewithHbAc.

    Hypertensionisassociatedwithplateletactivation andelevatedPMPslevelscomparedtonormalindividuals withacorrelationbetweenMPslevelsandbloodpres

    sure.SignificantcorrelationswerefoundbetweenPMPs. EMPsandbloodpressure.inelevatedMPs.EMPscould predictthehemodynamicseverity,Obesewomenhave significantlyhigherEMPsandPMPsnumbers.

    Microparticlesincardi0vasculardiseases: Inacutecoronarysyndrome,elevatedprocoagulant EMPsarefound.moreoverinthefirsthoursafteracute myocardialinfarction(MI)onset,therewasaninitialde. creaseofEMPs?plateletaggregates.,possiblybecause theseaggregatesaresequesteredintheinfraetedvesse1. AlthoughlevelsofEMPplateletaggregatesreturnedto

    valuesclosetothoseobservedinCAD48hoursafterthe acuteevent.ItwasdemonstratedthatahighEMPcount associateswithhighriskangiographiclesions.

    MPnumberscorrespondstotheseverity,lesionvol

    ume,andoutcomeinpatientswithstroke.Significantly higherEMPswerefoundinacuteischemicstroke, and

    increasedPMPswereobservedinpatientswithcerebral vaso.OCCusiveevents

    PMPsplaymainly

    sisdevelopment.TXA2

    animportantrolein

    originedfromPMPs

    atherosclero.

    canactivate

    ChineseJoumalofThrombosisandHemostasis2010Vol16No3 bothadjacentplateletsandECs.AlsoPMPsup-regulate adhesionmoleculesinECandenhancetheproductionof CDlla,andCD11binmonocytes,andECtransmigra- tion,andupregulateintercellularadhesionmolecule (ICAM.1)inhumanumbilica1veinECs.

    Venousthromboembolism:BothEMPsandEMP

    monocyteaggregatesareelevatedinvenousthromboem? bolism.ItwerefoundthathighPMPlevelscombined withhighD--dimerandP??selectinlevelscorrelatewith thediagnosisofdeepvenousthrombosis.

    Antiph0sphOlipidantibodysyndrome:Theendo- theliumisthetargetofantiphospholipidantibodies (aPL),elevatedEMPsarefoundinpatientswithaPL, butnotinpatientswithsystemiclupuserythematosus.It werefoundthatPMPsandEMPsaremoreelevatedin aPLpatientsthromboticdidordersthanwithout. Sepsis:Sepsisresultinperturbationsofcoagulation systemleadingtoDIC.Correspondingly,theremarkedly raislevelsofEMPs,PMPsandLMPs.ElevatedMPspre- dictoutcomesinpatientswithsepsisendothelialprotein Creceptor(EPCR)isexpressedonECsandmonocytes,

    ThesecellsreleaseEPCR??containingMPsduringstimula.- tedbyAPC.Thus,EMPsinthecirculatingbloodofsep

    ticpatientsmaypreictamorefavorableoutcome.Conse

    quentlyMPshaveoppositeeffectsinsepsis,depending ontheiroringinandsheddingmechanisms,presenceof anticoagulant(APC)orprocoagulant(PS,TF,vWF). Cancer:IncreasedMPswereassociatedwithmetas

    tasesincancer.ItwasreportedthatsomeMPshavea proangiogenicandarebelievedtoactastranscellular vectortopromoteorregulateangiogenesis.EMPsseemto haveametalloproteinaseeffect,lymphocyte-derivedMPs haveanegativeregulatoryeffectonangiogenesis,and PMPscouldexerttheireffectbyextracellularsignalrelat. edkinasepathways.

    TheMPsinbleedingdiseases:DecreaseMPswere foundinsomebleedingdiseases,forexceptCastaman syndromeandscottsyndrome.Inthisbleedingsyn

    drome,platelets,redbloodcellsandB.1ymphoblastsare defectiveinexternalizationItissupposedtobeduetoan underlyingdefiencyinphospholipidscramblaseenzyme. Miscellaneousdisorders:ElevatedMPshavebeen observedinthromboticthrombocytopenicpurpura,parox

    血栓与l卜血学2010年第l6卷第3

    ysmalnoeturnalhaemoglobinuria.sickleeellanemia.

    heparininducedthrombocytopenia,IHye1opro1iratiVe disorders,andinpregnancylossandpreeclampsia. TheroleofMPsinpathophysiologyofvariousdis

    easeprocessesisbeingextensivelyinvestigated.MPs mayreflectaphysiologicalelementoftheregulationof vascularandplateletfunction,andthefunctionalstateof

    parentalceilsandmayserveasamessengerofbiological signals.Infact,PMPsandpossiblyEMPsmaymarka prothromboticstate.LMPspredictedsubclinicalatero

    sclerosisburden.andelevatedEMPswerepredictiveof recurringMI.highPMPlevelswereindependentpredic

    torsofthromboticevents.FurthermoreMPsmayevenbe? cometherapeutictargetsforfuturetreatmentsofthrom

    boticdisorders.Thereaher,themeasurementofMPsbe

    ingregardedasapotentialbiomarker,giventherangeof conditionsinwhichtheyareelevatedandtheassociation withprothromboticstates.MPsofeancercelloriginasan earlymarkerfordetection/prognosisofmalignanciesis alsobeingexplored.Thereafter,measurementofmicrop

    articlesmayproveusefulasbiomarkersinevaluatingspe

    cificsituationssuchasendoyhelialdysfunctionandpro- thromboticstates.

    Ingenernal,elevatedMRsarethoughttoreflect clinicalconditions,butdefinitionofMPsonlybasedon }heirsizeisnotSUmeientandshouldbedescribedon theiroriginorbiologicaleffects.Thereforeapplicationon moremicroparticleparameterswillcontributetounder

    standtheelinicalsignificanceofthemeasurementofmi

    croparticles.Thesestudieshaveyettobefurtherexplora

    tionandresearch.

    (收稿日期:2010.O1.20)

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