0919国际期刊速递丨今日热点致心律

北京白癜风哪里治的好 http://baidianfeng.39.net/a_zczz/160124/4763965.html
TODAY今日发布JCardiovascMagnResonDec01,:21(1)今日发布01篇（共计60篇）IntJEmergMedDec01,:12(1)今日发布01篇（共计29篇）JAMAEarlyRecent,Sept18,今日发布02篇JAMACardiologyEarlyRecent,Sept18,今日发布09篇EURJCARDIOTHORACOct01,:56(4)今日发布29篇ATVBEarlyRecent,Sept19,今日发布04篇CirculationResearchEarlyRecent,Sept19,今日发布01篇CirculationEarlyRecent,Sept19,今日发布03篇RECOMMEND推荐阅读01致心律失常性心肌病免疫反应的治疗调节Circulationresearch-articleStephenP.Chelko,AngelikiAsimaki,etc.1小时前Background:Inflammationisaprominentfeatureofarrhythmogeniccardiomyopathy(ACM),butwhetheritcontributestothediseasephenotypeisnotknown.炎症是致心律失常性心肌病（ACM）的一个显著特征，但它是否与疾病表型有关尚不清楚。Methods:TodefinetheroleofinflammationinthepathogenesisofACM,wecharacterizedNFκBsignalinginACMmodelsinvitroandinvivo,andincardiacmyocytesfrompatientinducedpluripotentstemcells(hiPSCs).为了明确炎症在ACM发病机制中的作用，我们在ACM模型的体外和体内以及患者诱导的多能干细胞（hiPSCs）心肌细胞中研究了NFκB信号转导。Results:ActivationofNFκBsignaling,indicatedbyincreasedexpressionandnuclearaccumulationofphospho-RelA/p65,occurredinbothaninvitromodelofACM(expressionofJUPdel2inneonatalratventricularmyocytes),andinarobustmurinemodelofACM(homozygousknock-inofmutantdesmoglein-2;Dsg2mut/mut)thatrecapitulatesthecardiacmanifestationsseeninACMpatients.Bay11-,asmallmoleculeinhibitorofNFκBsignaling,preventeddevelopmentofACMdiseasefeaturesinvitro(abnormalredistributionofintercalateddiskproteins,myocyteapoptosis,releaseofinflammatorycytokines)andinvivo(myocardialnecrosisandfibrosis,LVcontractiledysfunction,ECGabnormalities).HeartsofDsg2mut/mutmiceexpressedmarkedlyincreasedlevelsofinflammatorycytokinesandchemotacticmoleculeswhichwereattenuatedbyBay11-.SalutaryeffectsofBay11-correlatedwiththeextenttowhichproductionofselectedcytokineshadbeenblocked.NFκBsignalingwasalsoactivatedincardiacmyocytesderivedfromapatientwithACM.Thesecellsproducedandsecretedabundantinflammatorycytokinesunderbasalconditions,andthiswasalsogreatlyreducedbyBay11-.NFκB信号转导的激活，由磷酸rela/p65的表达和核蓄积增加所指示，发生在ACM的体外模型（jupdel2在新生大鼠心室肌细胞中的表达）和ACM的健壮小鼠模型（突变桥粒蛋白-2的纯合敲入；Dsg2mut/mut），总结了ACM患者的心脏表现。BAY11-是NF-κB信号传导的小分子抑制剂，在体外（插入的盘蛋白的异常重新分布，心肌细胞凋亡，炎性细胞因子的释放）和在体（心肌坏死和纤维化，LV收缩功能障碍，心电图异常）阻止了ACM疾病特征的发展。Dsg2mut/mut小鼠心脏组织中炎性细胞因子和趋化分子的表达明显升高，Bay11-对其有明显的抑制作用。BAY11-的有益效果与所选细胞因子的产生被阻断的程度相关。NFκB信号在ACM患者心肌细胞中也被激活。这些细胞在基础条件下产生并分泌大量的炎性细胞因子，Bay11-也大大减少了这种现象。Conclusions:InflammatorysignalingisactivatedinACManditdriveskeyfeaturesofthedisease.Targetinginflammatorypathwaysmaybeaneffectivenewmechanism-basedtherapyforACM.炎症信号在ACM中被激活，并驱动疾病的关键特征。靶向炎症途径可能是一种有效的以机制为基础的治疗ACM的新方法。扫描

转载请注明：http://www.galanzweibolu.com/xjbzlyy/7294.html