Human scavenger protein AIM increases foam cell formation and CD36‐mediated oxLDL uptake

[摘要] AIMisexpressedbymacrophagesinresponsetoagonistsofthenuclearreceptorsLXR/RXR.Inmice,itactsasanatherogenicfactorbyprotectingmacrophagesfromtheapoptoticeffectsofoxidizedlipids.Inhumans,itisdetectedinatheroscleroticlesions,butnorolerelatedtoatherosclerosishasbeenreported.ThisstudyaimedtoinvestigatewhethertheroleofhAIMextendsbeyondinhibitingoxidizedlipid‐inducedapoptosis.Toaccomplishthisgoal,functionalanalysiswithhumanmonocyticTHP1cellsandmacrophagesdifferentiatedfromperipheralbloodmonocyteswereperformed.ItwasfoundthathAIMreducedoxLDL‐inducedmacrophageapoptosisandincreasedmacrophageadhesiontoendothelialICAM‐1byenhancingLFA‐1expression.Furthermore,hAIMincreasedfoamcellformation,asshownbyOilRedOandNileRedstaining,aswellasquantificationofcholesterolcontent.Thiswasnotaresultofdecreasedreversecholesteroltransport,ashAIMdidnotaffecttheeffluxsignificantlyfrom[3H]Cholesterol‐ladenmacrophagesdrivenbyplasma,apoA‐I,orHDL2acceptors.Rather,flowcytometrystudiesindicatedthathAIMincreasedmacrophageendocytosisoffluorescentoxLDL,whichcorrelatedwithanincreaseintheexpressionoftheoxLDLRCD36.Moreover,hAIMboundtooxLDLinELISAandenhancedthecapacityofHEK‐293cellsexpressingCD36toendocytoseoxLDL,asstudiedusingimmunofluorescencemicroscopy,suggestingthathAIMservestofacilitateCD36‐mediateduptakeofoxLDL.OurdatarepresentthefirstevidencethathAIMisinvolvedinmacrophagesurvival,adhesion,andfoamcellformationandsuggestasignificantcontributiontoatherosclerosis‐relatedmechanismsinthemacrophage...

[学科分类] 生理学

[关键词] CD5L;Spαmacrophage;atherosclerosis;apoptosis