Germans Menno R, Sun Wenhua, Sebök Martina, Keller Annika, Regli Luca
Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
World Neurosurg. 2022 Jan;157:143-151. doi: 10.1016/j.wneu.2021.10.114. Epub 2021 Oct 20.
The mechanisms of brain arteriovenous malformation (bAVM) development, formation, and progress are still poorly understood. By gaining more knowledge about the molecular signature of bAVM in relation to hemorrhage, we might be able to find biomarkers associated with this serious complication, which can function as a goal for further research and can be a potential target for gene therapy.
To provide a comprehensive overview of the molecular signature of bAVM-related hemorrhage We conducted a systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, of articles published in Embase, Medline, Cochrane central, Scopus, and Chinese databases (CNKI, Wanfang).
Our search identified 3944 articles, of which 3108 remained after removal of duplicates. After title, abstract, and full-text screening, 31 articles were included for analysis. The results show an overview of molecular characteristics. Several genetic polymorphisms are identified that increase the risk of bAVM rupture by increasing the expression of certain inflammatory cytokines (interleukin [IL]-6, IL-17A, IL-1β, and tumor necrosis factor-α), NOTCH pathways, matrix metalloproteinase-9, and vascular endothelial growth factor-α.
Several molecular factors are associated with the risk of bAVM-related hemorrhage. These factors are associated with increased inflammation on the cellular level and changes in the endothelium leading to instability of the vessel wall. Further investigation of these biomarkers regarding hemorrhage rates, together with their relationship with noninvasive diagnostic methods, should be a goal of future studies to improve the patient specific risk estimation and future treatment options.
脑动静脉畸形（bAVM）的发生、形成和进展机制仍未完全明确。通过深入了解与出血相关的bAVM分子特征，我们或许能够找到与这种严重并发症相关的生物标志物，这些标志物可作为进一步研究的目标以及基因治疗的潜在靶点。
全面概述与bAVM相关出血的分子特征。我们按照系统评价和Meta分析的首选报告项目指南，对发表在Embase、Medline、Cochrane中心、Scopus和中文数据库（CNKI、万方）中的文章进行了系统评价。
我们的检索共识别出3944篇文章，去除重复项后剩余3108篇。经过标题、摘要和全文筛选，纳入31篇文章进行分析。结果展示了分子特征的概述。已识别出几种基因多态性，它们通过增加某些炎性细胞因子（白细胞介素[IL]-6、IL-17A、IL-1β和肿瘤坏死因子-α）、NOTCH信号通路、基质金属蛋白酶-9和血管内皮生长因子-α的表达来增加bAVM破裂的风险。
几种分子因素与bAVM相关出血的风险有关。这些因素与细胞水平上炎症增加以及内皮变化导致血管壁不稳定有关。进一步研究这些出血率生物标志物及其与非侵入性诊断方法的关系，应是未来研究的目标，以改善针对患者的风险评估和未来治疗方案。
