脂蛋白(a)在炎症病人中的变化

脂蛋白(a)在炎症病人中的变化

Introduction

Lipoprotein(a)orLp(a)isatypeoflipoproteinthathasbeenassociatedwithcardiovasculardiseasefordecades.Itisauniquetypeoflipoproteinasitcontainsbothalow-densitylipoprotein(LDL)-likeparticleandanotherglycoproteincalledapolipoprotein(a).Lp(a)hasseveralphysiologicalfunctions,includingthemodulationofcoagulationandfibrinolysis,aswellasinflammation.TherehavebeenreportsthatLp(a)levelsareelevatedinindividualswithchronicinflammation,buttheexactmechanismsarenotwellunderstood.ThispaperaimstoexplorethevariationsinLp(a)levelsinpatientswithinflammationandthepossiblemechanisms.

FactorsthataffectLp(a)concentrationsinpatientswithinflammation

ThereareseveralknownfactorsthatcanaffectLp(a)concentrationsinpatientswithinflammation.Thesefactorsincludecytokines,adipokines,lipids,andhepaticsynthesisandmetabolism.

Cytokines,whicharesignalingmoleculesproducedbyimmuneandnon-immunecellsduringaninflammatoryresponse,havebeenshowntoincreaseLp(a)levels.Interleukin-6(IL-6)isapro-inflammatorycytokinethathasbeenshowntoincreaseLp(a)synthesisinhepatocytes.Tumornecrosisfactor-alpha(TNF-α)isanotherpro-inflammatorycytokinethathasbeenshowntoincreaseLp(a)serumconcentrationsinanimalmodels.

Adipokinesarecytokinessecretedbyadiposetissueandplayaroleintheregulationofenergyhomeostasisandinflammation.Adiponectin,atypeofadipokine,hasanti-inflammatorypropertiesandisnegativelycorrelatedwithLp(a)levels.Leptin,anotheradipokine,haspro-inflammatorypropertiesandispositivelycorrelatedwithLp(a)levels.

Lipids,particularlyLDLcholesterol,havealsobeenlinkedtoLp(a)levels.HighlevelsofLDLcholesterolcanleadtoincreasedLp(a)synthesisasthetwolipoproteinscompeteforthesamereceptoronthehepatocytemembrane.

HepaticsynthesisandmetabolismalsoplayaroleinLp(a)levelsinpatientswithinflammation.HepaticproductionistheprimarysourceofLp(a)inthecirculation,andfactorsthatincreaseliversynthesiscanleadtoincreasedLp(a)levels.Hepaticmetabolism,ontheotherhand,canaffecttheclearanceofLp(a)fromthecirculation,whichcanresultinelevatedLp(a)levels.

ImpactofinflammationonLp(a)concentrations

SeveralstudieshavereportedtheimpactofinflammationonLp(a)concentrations.Forexample,ithasbeenreportedthatpatientswithrheumatoidarthritishavehigherLp(a)levelsthanhealthysubjects.InflammatoryboweldiseasepatientsalsohavehigherLp(a)levelsthanhealthycontrols.Patientswithchronickidneydisease,whooftenhaveachroniclow-gradeinflammatorystate,haveelevatedLp(a)levels.AstudyalsoshowedthatLp(a)levelswerehigherinpatientswithsystemiclupuserythematosusthaninhealthycontrols.

MechanismsofLp(a)ininflammation

Lp(a)hasbeenshowntoplayaroleininflammation,althoughtheexactmechanismsarenotwellunderstood.OnehypothesisisthatLp(a)mayactasapro-inflammatorymoleculebybindingtobacterialendotoxinsandtriggeringthereleaseofpro-inflammatorycytokines.AnotherhypothesisisthatLp(a)maypromoteinflammationbyinhibitingthefibrinolyticsystem,whichcanleadtochronicinflammation.Moreover,Lp(a)canalsocontributetothedevelopmentofatherosclerosisbybindingtooxidizedLDLcholesterolandpromotingfoamcellformation.

TreatmentoptionsforelevatedLp(a)levelsininflammation

ThereisnospecifictreatmentforelevatedLp(a)levelsinpatientswithinflammation.However,severaltreatmentoptionsforreducinginflammationandpreventingcardiovasculardiseasemayalsoleadtoareductioninLp(a)levels.Theseoptionsincludelifestylemodificationssuchasweightloss,exercise,andahealthydiet,aswellastheuseofanti-inflammatorydrugssuchasnonsteroidalanti-inflammatorydrugs(NSAIDs)andbiologicagentssuchasanti-tumornecrosisfactor-alpha.

Conclusion

ElevatedLp(a)levelshavebeenreportedinpatientswithinflammation,buttheexactmechanismsarenotwellunderstood.Severalfactors,includingcytokines,adipokines,lipids,andhepaticsynthesisandmetabolism,canaffectLp(a)concentrationsinpatientswithinflammation.Lp(a)hasbeenshowntoplayaroleininflammation,althoughtheexactmechanismsareyettobefullyelucidated.ThereiscurrentlynospecifictreatmentforelevatedLp(a)levelsinpatientswithinflammation,butmitigatinginflammationan