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Effects of Murine Norovirus on Atherosclerosis in Ldlr–/–Mice Depends on the Timing of Infection

机译:鼠诺如病毒对Ldlr //#8211;小鼠动脉粥样硬化的影响取决于感染的时机。

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Wepreviouslyreportedthatmurinenorovirus(MNV),avirusprevalentinUnitedStatesresearchinstitutions,increasedatheroscleroticlesionsizeinLdlrsup#8211;/#8211;/supmicewhenthemicewereinfected8wkafterfeedinganatherogenicdiet.TodeterminewhetherthetimingofMNVinfectionrelativetoatherosclerosisdevelopmentalteredthediseasephenotypeandtoexaminepotentialmechanismsbywhichMNVinfluencesthediseaseprocess,wefedLdlrsup#8211;/#8211;/supmiceanatherogenicdietfor16wk.Threedaysafterinitiatingtheatherogenicdiet,halfofthemicereceivedMNV4andtheotherhalfvehicleonly(clarifiedcell-culturelysate;controls).Bothgroupsofmicedevelopedlargeaorticsinuslesions(controlcomparedwithMNV4:133±8×10sup3/sup#956;msup2/supcomparedwith140±7×10sup3/sup#956;msup2/sup)thatwerenotsignificantlydifferentinsize.BecausethetimingofMNVinfectionrelativetoatherosclerosisdevelopmentandhypercholesterolemiadifferedbetweenourpreviousandthecurrentstudies,weexaminedwhetherhypercholesterolemiaalteredMNV4-inducedchangesinbone-marrow#8211;derivedmacrophages.MNV4infectionincreasedthepotentialofmacrophagestotakeupandstorecholesterolbyincreasingCD36expressionwhilesuppressingtheABCA1transporter.Thus,theeffectsofMNV4infectiononatheroscleroticlesionsizeappeartobedependentonthetimingoftheinfection:MNV4infectionpromotesonlyestablishedlesions.ThiseffectmaybeduetoMNV4'sabilitytoincreasecholesteroluptakeanddecreaseeffluxbyregulatingCD36andABCA1proteinexpression.
机译:Wepreviouslyreportedthatmurinenorovirus(MNV),avirusprevalentinUnitedStatesresearchinstitutions,increasedatheroscleroticlesionsizeinLdlr #8211; /#8211; micewhenthemicewereinfected8wkafterfeedinganatherogenicdiet.TodeterminewhetherthetimingofMNVinfectionrelativetoatherosclerosisdevelopmentalteredthediseasephenotypeandtoexaminepotentialmechanismsbywhichMNVinfluencesthediseaseprocess,wefedLdlr #8211; /#8211; miceanatherogenicdietfor16wk.Threedaysafterinitiatingtheatherogenicdiet,halfofthemicereceivedMNV4andtheotherhalfvehicleonly(clarifiedcell-culturelysate ;两组小鼠都出现了较大的主动脉病变(与MNV4相比:133±8×10 3 #956; m 2 与140±7×10 3 #956; m 2 )在大小上没有显着差异。由于相对于动脉粥样硬化发展和高胆固醇血症的MNV感染的时机与以前的研究和当前研究之间存在差异,因此我们检查了高胆固醇血症改变的MNV4引起的骨髓内改变#8211;衍生的巨噬细胞.MNV4感染通过增加CD36的表达同时抑制ABCA1转运蛋白而增加了巨噬细胞摄取和储存胆固醇的潜能。因此,MNV4感染对动脉粥样硬化的影响大小似乎取决于蛋白酶4的表达并确定了蛋白酶4的影响力,这决定了MNV4感染率的升高决定了MNV4感染的可能性。

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