1121国际期刊速递丨今日热点静脉血

TODAY今日发布CurrAtherosclerRepDec01,:21(12)今日发布02篇（共计07篇）CurrCardiovascImagingRepDec01,:12(12)今日发布02篇CardiolTherEarlyRecent,Nov20,今日发布01篇JThrombThrombolysisEarlyRecent,Nov21,今日发布01篇EURHEARTJNov21,:40(44)今日发布21篇EuropeanHeartJournal-CardiovascularImagingDec01,:20(12)今日发布21篇CirculationEarlyRecent,Nov21,今日发布02篇JAHADec03,:8(23)今日发布04篇（共计08篇）ATVBEarlyRecent,Nov21,今日发布02篇CirculationResearchEarlyRecent,Nov21,今日发布01篇RECOMMEND推荐阅读01激活内皮TGFβ1信号通过内皮素1促进小鼠静脉血栓不溶解：慢性血栓栓塞性肺动脉高压的潜在作用CirculationResearchresearch-articleMagdalenaLudmilaBochenek,ChristianeLeidinger,etc.1小时前等42用户推荐阅读本文Rationale:Chronicthromboembolicpulmonaryhypertension(CTEPH)ischaracterizedbydefectivethrombusresolution,pulmonaryarteryobstructionandvasculopathy.Transforminggrowthfactor-beta(TGFβ)signalingmutationshavebeenimplicatedinpulmonaryarterialhypertension,whereasTGFβsroleinthepathophysiologyofCTEPHisunknown.慢性血栓栓塞性肺动脉高压（CTEPH）以血栓溶解不良、肺动脉阻塞和血管病变为特征。转化生长因子β（TGFβ）信号突变与肺动脉高压有关，而TGFβ在CTEPH病理生理中的作用尚不清楚。Objective:TodeterminewhetherdefectiveTGFβsignalinginendothelialcellscontributestothrombusnon-resolutionandfibrosis.探讨内皮细胞TGFβ信号转导缺陷是否与血栓不溶解和纤维化有关。MethodsandResults:VenousthrombosiswasinducedbyinferiorvenacavaligationinmicewithgeneticdeletionofTGFβ1inplatelets(Plt.TGFβ-KO)orTGFβtypeIIreceptorsinendothelialcells(End.TGFβRII-KO).PulmonaryendarterectomyspecimensfromCTEPHpatientswereanalyzedusingimmunohistochemistry.Primaryhumanandmouseendothelialcellswerestudiedusingconfocalmicroscopy,quantitativePCRandwesternblot.AbsenceofTGFβ1inplateletsdidnotalterplateletnumberorfunction,butwasassociatedwithfastervenousthrombusresolution,whereasendothelialTGFβRIIdeletionresultedinlarger,morefibroticandhighervascularizedvenousthrombi.IncreasedcirculatingactiveTGFβ1levels,endothelialTGFβRI/ALK1andTGFβRI/ALK5expressionweredetectedinEnd.TGFβRII-KOmice,andactivatedTGFβsignalingwaspresentinvessel-richareasofCTEPHspecimens.CTEPH-ECsandmurineendothelialcellslackingTGFβRIIsimultaneouslyexpressedendothelialandmesenchymalmarkersandtranscriptionfactorsregulatingendothelial-to-mesenchymaltransition,similartoTGFβ1-stimulatedendothelialcells.Mechanistically,increasedendothelin-1levelsweredetectedinTGFβRII-KOendothelialcells,murinevenousthrombiorendarterectomyspecimensandplasmaofCTEPHpatients,andendothelin-1overexpressionwaspreventedbyinhibitionofALK5,andtoalesserextentofALK1.ALK5inhibitionandendothelinreceptorantagonizationinhibitedmesenchymallineageconversioninTGFβ1-exposedhumanandmurineendothelialcellsandimprovedvenousthrombusresolutionandpulmonaryvaso-occlusionsinEnd.TGFβRII-KOmice.结扎小鼠下腔静脉诱发静脉血栓形成，血小板TGFβ1基因缺失（Plt，TGFβ-KO）或内皮细胞TGFβⅡ型受体基因缺失（End，TGFβRII-KO）。应用免疫组化方法分析CTEPH患者肺动脉内膜切除术标本。采用共聚焦显微镜、定量PCR和westernblot对人和小鼠原代内皮细胞进行了研究。血小板中TGFβ1的缺失并不改变血小板的数量和功能，但与更快的静脉血栓溶解有关，而内皮TGFβRII缺失导致更大、更纤维化和更高的血管化静脉血栓。循环活动性TGFβ1水平升高，内皮细胞TGFβRI/ALK1和TGFβRI/ALK5表达增加，TGFβRII-KO小鼠，CTEPH标本血管丰富区存在激活的TGFβ信号传导。CTEPH-ECs和缺乏TGFβRII的小鼠内皮细胞同时表达内皮和间充质标志物以及调控内皮向间充质转化的转录因子，类似于TGFβ1刺激的内皮细胞。在机制上，CTEPH患者的TGFβRII-KO内皮细胞、小鼠静脉血栓或动脉内膜切除标本和血浆中检测到内皮素-1水平升高，抑制ALK5可阻止内皮素-1的过度表达，并在较小程度上抑制ALK1。ALK5抑制和内皮素受体拮抗可抑制TGFβ1暴露的人和小鼠内皮细胞间充质系转化，并最终改善TGFβRII-KO小鼠的静脉血栓溶解和肺血管阻塞。Conclusions:EndothelialTGFβ1signalingviatypeIreceptorsandendothelin-1contributetomesenchymallineagetransitionandthrombofibrosis,whichwerepreventedbyblockingendothelinreceptors.OurfindingsmayhaverelevantimplicationsforthepreventionandmanagementofCTEPH.内皮细胞TGFβ1信号转导途径I型受体和内皮素-1参与间充质细胞的分化和血栓纤维化，通过阻断内皮素受体而得以阻止。我们的发现可能对CTEPH的预防和治疗有一定的意义。扫描