TY - T1的内腔活检的分子分析人类大脑血管畸形JF -神经学乔-神经病学SP - e1637 LP - e1647做- 10.1212 / WNL。首页0000000000200109六世- 98 - 16 AU -伊桑温克勒盟吴振伟AU -尤金·吉尔AU -大卫·麦科伊盟Kazim Narsinh AU -正大阳光盟Kerstin穆勒盟杰登·罗斯AU -海伦金盟Shantel Weinsheimer AU - Mitchel伯杰盟Tomasz Nowakowski AU -丹尼尔Lim盟阿迪Abla AU -丹尼尔·库克Y1 2022/04/19 UR - //www.ez-admanager.com/content/98/16/e1637.abstract N2 Ras-mitogen-activated背景和目标蛋白激酶(MAPK)信号异常发生在大部分脑动静脉畸形(bAVMs)。首页不存在分子概要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描述基因表达和血液流量介导的转录变化生活的病人。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。 Endoluminal biopsy yielded 269.0 ± 79.9 cells per biopsy (control 309.2 ± 86.6 cells, bAVM 228.8 ± 133.4 cells). 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 ER -