title: Immunohistochemical Analysis of Sox17 Associated Pathway in Brain Arteriovenous Malformations.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yulius
authors.initials: Y
authors.lastname: Hermanto
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: ytakagi@kuhp.kyoto-u.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takagi
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ishii
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Funaki
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mineharu
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002536:Cerebral Arteries / Q000378:metabolism / Q000473:pathology; D002550:Cerebral Veins / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D002538:Intracranial Arteriovenous Malformations / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000378:metabolism* / Q000473:pathology*; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D018932:Chemokine CCL2; D055760:SOXF Transcription Factors; D051176:beta Catenin; C485631:HEY1 protein, human; C109188:SOX17 protein, human
keywords: Arteriovenous malformation; Hey1; Sox17; Vascular remodeling; β-catenin