Immunohistochemical Analysis of Sox17 Associated Pathway in Brain Arteriovenous Malformations.
Immunohistochemical Analysis of Sox17 Associated Pathway in Brain Arteriovenous Malformations.
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DOI：
10.1016/j.wneu.2015.10.003
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发表时间：
2016-03
影响因子：
2
通讯作者：
Y. Hermanto;Y. Takagi;A. Ishii;Kazumichi Yoshida;T. Kikuchi;T. Funaki;Y. Mineharu;S. Miyamoto
中科院分区：
文献类型：
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作者：
Y. Hermanto;Y. Takagi;A. Ishii;Kazumichi Yoshida;T. Kikuchi;T. Funaki;Y. Mineharu;S. Miyamoto
sox17已成为血管重构的一个重要因子，因为它与Wnt/β-catenin、Notch和炎症通路有潜在的联系。脑动静脉畸形（BAVM）作为一种血管生成和炎症性疾病，可能存在Sox17相关通路的异常调控。我们试图研究Sox17相关通路在bavm中的表达。方法采用免疫组织化学方法对16例BAVM病灶石蜡标本进行分析。标本是在手术过程中从患者身上获得的。结果所有标本中均有Sox17、Hey1、β-catenin的表达。大的静脉具有明显的表现模式；Sox17、Hey1和β-catenin在厚壁静脉中的表达强度较强，薄壁静脉中的表达强度较弱（P< 0.001）。厚壁静脉中Sox17、Hey1、β-catenin的表达也高于大动脉（P< 0.05）。Hey1和β-catenin在厚壁静脉中的表达也高于脑微血管（P< 0.01）。此外，中、小动脉中Sox17相关通路Hey1和β-catenin的表达与大动脉中BAVM病灶和脑微血管的表达差异有统计学意义（P< 0.01）。结论在BAVM病灶中Sox17相关通路被激活。我们的结果表明，在厚壁静脉中获得了动脉身份；这可能反映了血流动力学应力导致静脉动脉化的过程。此外，Sox17相关通路在中小动脉中的高表达表明BAVM血管具有内在活性。
BackgroundSox17 has emerged as an important factor in vascular remodeling because of the potential linkage with Wnt/β-catenin, Notch, and the inflammatory pathway. Brain arteriovenous malformation (BAVM), as an angiogenic and inflammatory disorder, might possess an aberrant regulation of the Sox17 associated pathway. We sought to investigate the expression of the Sox17 associated pathway in BAVMs.MethodsUsing immunohistochemical methods, 16 paraffin specimens of BAVM nidus were analyzed. Specimens were obtained from patients during surgical procedures.ResultsExpression of Sox17, Hey1, and β-catenin was observed in all specimens. Large veins possessed a distinct pattern of expression; thick-walled veins had a stronger intensity, whereas thin-walled veins had a weaker intensity, of Sox17, Hey1, and β-catenin (P< 0.001). Thick-walled veins also had a higher expression of Sox17, Hey1, and β-catenin compared with large arteries (P< 0.05). Hey1 and β-catenin expression was also higher in thick-walled veins compared with brain microvessels (P< 0.01). In addition, the difference in expression of the Sox17 associated pathway (Hey1 and β-catenin) was observed in medium and small arteries compared with large arteries in BAVM nidus and brain microvessels (P< 0.01).ConclusionsThe Sox17 associated pathway was activated in the BAVM nidus. Our results indicate that arterial identity is gained in thick-walled veins; this might reflect the process of arterialization of the veins as a result of hemodynamic stress. In addition, high expression of the Sox17 associated pathway in medium and small arteries indicates that BAVM vessels are intrinsically active.