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

[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...

[学科分类] 生理学

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