Immunohistochemical Analysis of Sox17 Associated Pathway in Brain Arteriovenous Malformations

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• 作者：Yulius Hermanto ; Yasushi Takagi ; ^{ytakagi@kuhp.kyoto-u.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Akira Ishii ; Kazumichi Yoshida ; Takayuki Kikuchi ; Takeshi Funaki ; Yohei Mineharu ; Susumu Miyamoto
• 关键词：Arteriovenous malformation ; β-catenin ; Hey1 ; Sox17 ; Vascular remodeling
• 刊名：World Neurosurgery
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：87
• 期：Complete
• 页码：573-583.e2
• 全文大小：8663 K

文摘

Sox17 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.

Methods

Using immunohistochemical methods, 16 paraffin specimens of BAVM nidus were analyzed. Specimens were obtained from patients during surgical procedures.

Results

Expression 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).

Conclusions

The 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.