Diet‐induced (epigenetic) changes in bone marrow augment atherosclerosis

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: DNA methylation;    Pu.1;    IRF8;    hematopoiesis;    macrophage;    CpG island;   

DOI  :  10.1189/jlb.1A0114-017R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

AlterationsinDNAmethylationpatternsinperipheralbloodleukocytesprecedeatheroscleroticlesiondevelopmentinmousemodelsofatherosclerosisandhavebeenlinkedtocardiovasculardeathinpatients.Theaimofthisstudyistoinvestigatethelong‐termchangesinducedbyWTDfeedingonBMcellsandtheconsequencesforatherosclerosissusceptibility.Hereto,WTDBMorChowBMwastransplantedintoLDLRKOmiceonchow.BMfromWTDBMrecipientmiceexhibitedhypomethylationofCpGregionsinthegenesencodingPu.1andIRF8,keyregulatorsofmonocyteproliferationandmacrophagedifferentiation.Inagreement,inblood,thenumbersofleukocyteswere40%(P<0.05)higherasaresultofanincreaseinF4/80+monocytes(3.4‐fold;P<0.01).AnincreaseofCD11c++cellswasalsofound(2.4‐fold;P<0.05).Furthermore,spleenswereenlarged,andthepercentageofF4/80+cellsexpressingCD86wasinduced(1.8‐fold;P<0.01),indicatingincreasedactivationofsplenicmacrophages.Importantly,micereconstitutedwithWTDBMshowedasignificant,1.4‐fold(P<0.05)increaseinaorticrootplaquesizeintheabsenceofchangesinserumcholesterol.WeconcludethatWTDchallengeinducestransplantableepigeneticchangesinBM,alterationsinthehematopoieticsystem,andincreasedsusceptibilitytoatherosclerosis.Manipulationoftheepigenome,whenusedinconjunctionwithbloodlipidreduction,couldthusprovebeneficialtotreatcardiovasculardisorders...

【 授权许可】

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