title: Biological relevance of tissue factor and IL-6 in arteriovenous malformations.
abstract: Arteriovenous malformations (AVMs) are congenital abnormal vessels that shunt blood directly from the arterial to the venous system without a capillary bed. The underlying pathology of AVMs is not fully understood. The objective of the study was to determine the association between the expression patterns of tissue factor (TF) and interleukin-6 (IL-6) in AVMs with clinical and pathological findings. Eighteen cases of sporadic AVM with operative specimens were included in this study. The expression of messenger RNA (mRNA) of TF and IL-6 was assayed, and association with clinical factors was investigated. The distribution of TF and IL-6 was examined with immunofluorescence. The mRNA expression of TF was significantly higher in AVM specimens than in control tissues (P = 0.002) and significantly higher in the symptomatic group than in the asymptomatic group (P = 0.037). The mRNA expression of IL-6 was likewise significantly higher in AVM specimens than in control tissues (P = 0.038). Examination of immunostained sections indicated that TF+cells were also positive for IL-6 and were distributed around normal endothelial cells and pericytes. Moreover, TF+/IL-6+cells also expressed CD31, vascular endothelial growth factor receptor 2 (VEGFR2), and platelet-derived growth factor receptor beta (PDGFR-beta). These results suggest that TF is elevated in AVMs and that it mediates symptomatic events. IL-6 is associated with the angiogenic activity of TF, and both are present in the same abnormal endothelial cells and pericytes. These factors may have interactive effects and may serve in a prognostic role for AVMs.
authors.affiliation: Department of Neurosurgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.|Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan.
authors.forename: Shouhei
authors.initials: S
authors.lastname: Noshiro
authors.affiliation: Department of Neurosurgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan. tmikami@sapmed.ac.jp.|Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan. tmikami@sapmed.ac.jp.
authors.forename: Takeshi
authors.identifier: http://orcid.org/0000-0002-8608-1037
authors.initials: T
authors.lastname: Mikami
authors.affiliation: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kataoka-Sasaki
authors.affiliation: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan.|Department of Neurology, Yale University School of Medicine, New Haven, CT, 06510, USA.|Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT, 06516, USA.
authors.forename: Masanori
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hashi
authors.affiliation: Department of Neurosurgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.|Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Ohtaki
authors.affiliation: Department of Neurosurgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.|Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Wanibuchi
authors.affiliation: Department of Neurosurgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Mikuni
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, 06510, USA.|Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT, 06516, USA.
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Kocsis
authors.affiliation: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan.|Department of Neurology, Yale University School of Medicine, New Haven, CT, 06510, USA.|Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT, 06516, USA.
authors.forename: Osamu
authors.initials: O
authors.lastname: Honmou
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002196:Capillaries; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D002538:Intracranial Arteriovenous Malformations / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics; D013925:Thromboplastin / Q000235:genetics* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D013925:Thromboplastin; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Cerebral arteriovenous malformations; Endothelial cell; Interleukin-6; Tissue factor