@article {Winklere1637作者={伊桑温克勒吴振伟和尤金·吉尔和大卫·麦考伊Kazim Narsinh正大阳光Kerstin穆勒和杰登·罗斯金和海伦和Shantel Weinsheimer Mitchel伯杰和Tomasz Nowakowski丹尼尔Lim和阿迪Abla和丹尼尔·库克},title ={内腔活检的分子分析人类大脑血管畸形},体积={98}={16},页面= {e1637——e1647} = {2022}, doi = {10.1212 / WNL。出版商0000000000200109}= {Wolters Kluwer健康,公司代表美国神经病学学会},抽象的Ras {\ textendash} ={背景和目标增殖蛋白激酶(MAPK)信号首页异常发生在大部分脑动静脉畸形(bAVMs)。不存在分子概要bAVMs没有开放手术,限制精密医学治疗方法。在这里,我们报告使用血管内腔的内腔活检bAVMs描述基因表达和血流{\ textendash}介导转录住病人的变化。内腔活检方法和计算流体动力学(CFD)进行建模与脑血管造影术成人颅内动静脉。每个病人接受手术切除和细胞从连续的动脉段采样。Fluorescence-assisted细胞分选富集内皮细胞,测序Illumina公司4000年HiSeq编曲。基因表达与RNA序列量化(RNAseq)。差异基因表达、本体论和相关分析。结果验证和定量逆转录聚合酶链反应(RT-qPCR)。内腔活检结果是成功没有并发症4例。内腔活检取得269.0 {\ textpm} 79.9细胞活检(控制309.2 {\ textpm} 86.6细胞,bAVM 228.8 {\ textpm} 133.4细胞)。 RNAseq identified 106 differentially expressed genes (DEGs) in bAVMs (false discovery rate <=0.05). DEGs were enriched for bAVM pathogenic cascades, including Ras-MAPK signaling (p \< 0.05), and confirmed with RT-qPCR and a panel predictive of MAPK/extracellular signal-regulated kinase inhibitor response. Compared to patient-matched surgically excised tissues, endoluminal biopsy detected 83.3\% of genes, and genome-wide expression strongly correlated (Pearson r = 0.77). Wall shear stress measured by CFD correlated with inflammatory pathway upregulation. Comparison of pre-embolization and postembolization samples confirmed flow-mediated gene expression changes.Discussion Endoluminal biopsy allows molecular profiling of bAVMs in living patients. Gene expression profiles are similar to those of tissues acquired with open surgery and identify potentially targetable Ras-MAPK signaling abnormalities in bAVMs. Integration with CFD allows determination of flow-mediated transcriptomic alterations. Endoluminal biopsy may help facilitate trials of precision medicine approaches to bAVMs in humans.AVM=arteriovenous malformation; bAVM=brain AVM; CBF=cerebral blood flow; CFD=computational fluid dynamic; DEG=differentially expressed gene; DSA=digital subtraction angiography; FACS=fluorescence-activated cell sorting; FDR=false discovery rate; MAPK=mitogen-activated protein kinase; MEK=MAPK/extracellular signal-regulated kinase; qPCR=quantitative PCR; RNAseq=RNA sequencing; scRNAseq=single-cell RNAseq; TAWSS=time-averaged wall shear stress; 3D=3-dimensional}, issn = {0028-3878}, URL = {//www.ez-admanager.com/content/98/16/e1637}, eprint = {//www.ez-admanager.com/content/98/16/e1637.full.pdf}, journal = {Neurology} }