北京哪有白癜风专科医院 http://yyk.39.net/bj/zhuanke/89ac7.htmlTODAY今日发布BMCCardiovascDisordDec01,:19(1)今日发布01篇（共计篇）CardiovascDrugsTherEarlyRecent,May08,今日发布02篇HeartFailRevEarlyRecent,May08,今日发布01篇CirculationResearchEarlyRecent,May08,今日发布01篇RECOMMEND推荐阅读01线粒体是激活单核细胞释放的细胞外小泡的一个子集，在内皮细胞中诱导I型干扰素和TNF反应。CirculationResearchresearch-articleFlorianPuhm,TarasAfonyushkin,etc.2小时前Rationale:Extracellularvesicles,includingmicrovesicles(MVs),areincreasinglyrecognizedasimportantmediatorsincardiovasculardisease.Thecargoandsurfaceproteinstheycarryareconsideredtodefinetheirbiologicalactivity,includingtheirinflammatoryproperties.Monocytetoendothelialcellsignalingisaprerequisiteforthepropagationofinflammatoryresponses.However,thecontributionofMVsinthisprocessispoorlyunderstood.细胞外囊泡，包括微囊泡（MVS），越来越被认为是心血管疾病的重要介质。它们携带的货物和表面蛋白质被认为是定义它们的生物活性，包括它们的炎症性质。单核细胞到内皮细胞的信号传导是炎症反应传播的先决条件。然而，对MVS在这一过程中的贡献知之甚少。Objective:ToelucidatethemechanismsbywhichMVsderivedfromactivatedmonocyticcellsexertinflammatoryeffectsonendothelialcells.目的探讨活化单核细胞产生的MVS对内皮细胞的炎症作用机制。MethodsandResults:LPS-stimulatedmonocyticcellsreleasefreemitochondriaandMVswithmitochondrialcontentasdemonstratedbyflowcytometry,quantitativePCR,WesternBlotandtransmissionelectronmicroscopy.UsingRNAseqanalysisandqRT-PCRwedemonstratedthatbothmitochondriadirectlyisolatedfromandMVsreleasedbyLPS-activatedmonocyticcells,aswellascirculatingMVsisolatedfromvolunteersreceivinglow-doseLPS-injections,inducetypeIInterferonandTNFresponsesinendothelialcells.DepletionoffreemitochondriasignificantlyreducedtheabilityoftheseMVstoinducetypeIInterferonandTNF-dependentgenes.Weidentifiedmitochondria-associatedTNFandRNAfromstressedmitochondriaasmajorinducersofthesetworesponses.Finally,wedemonstratedthattheproinflammatorypotentialofMVsanddirectlyisolatedmitochondriawasdrasticallyreducedwhentheywerederivedfrommonocyticcellswithnon-respiringmitochondriaormonocyticcellsculturedinthepresenceofpyruvateorthemitochondrialROSscavengerMitoTEMPO.流式细胞术、定量PCR、Westernblot和透射电镜显示，LPS刺激的单核细胞释放游离线粒体和线粒体含量高的MVS。利用RNaseq分析和qrt-pcr，我们证明了从LPS激活的单核细胞中直接分离的线粒体和释放的MVS，以及从接受低剂量LPS注射的志愿者中分离的循环MVS，在内皮细胞中诱导I型干扰素和TNF反应。游离线粒体的缺失显著降低了MVS诱导I型干扰素和TNF依赖基因的能力。我们发现线粒体相关的TNF和RNA是这两种反应的主要诱导物。最后，我们证明，当MVS和直接分离的线粒体来源于具有无呼吸线粒体的单核细胞或在丙酮酸盐或线粒体活性氧清除剂mitotempo存在下培养的单核细胞时，它们的促炎潜能显著降低。Conclusions:MitochondriaandmitochondriaembeddedinMVsconstituteamajorsubsetofextracellularvesiclesreleasedbyactivatedmonocytesandtheirproinflammatoryactivityonendothelialcellsisdeterminedbytheactivationstatusoftheirparentalcells.Thus,mitochondriamayrepresentcriticalintercellularmediatorsincardiovasculardiseaseandotherinflammatorysettingsassociatedwithtypeIIFNandTNFsignaling.MVS中的线粒体和线粒体是激活单核细胞释放的细胞外囊泡的主要亚群，其对内皮细胞的促炎活性由其亲本细胞的激活状态决定。因此，线粒体可能是心血管疾病和与I型干扰素和TNF信号相关的其他炎症环境中的关键细胞间介质。扫描