title: Co-expression of tissue factor and IL-6 in immature endothelial cells of cerebral cavernous malformations.
abstract: Cerebral cavernous malformations (CCMs) are congenital abnormal clusters of capillaries that are prone to leaking and thought to result from a disorder of endothelial cells. The underlying pathology of CCM is not fully understood. We analyzed the expression of tissue factor (TF) and interleukin-6 (IL-6) in CCMs to determine the association of TF and IL-6 with clinical and pathological findings. Thirteen cases of operative specimens of sporadic CCMs were included in this study. The expression of messenger RNA of TF and IL-6 was assayed and the association with clinical factors was investigated. Then, the distribution of TF and IL-6 was examined with immunofluorescence. The mRNA expression of TF of CCMs was significantly higher than that of the control (p=0.017), and was correlated with the number of hemorrhage appearances (p=0.190, ρ=0.62). The mRNA expression level of IL-6 was significantly correlated with the mRNA expression level of TF (p=0.034, ρ=0.58). Examination of immunostained sections indicated that TF+cells were also positive for IL-6, and distributed around normal endothelial cells. Moreover, the TF+/IL-6+cells expressed CD31 and VEGFR2. The expressions of IL-6 and TF were correlated, and both were present in the same immature endothelial cells. TF is elevated in CCM and might mediate progressive events. These factors may play a prognostic role in CCM.
authors.affiliation: Department of Neurosurgery, Sapporo Medical University, School of Medicine, Japan; Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University, School of Medicine, Japan.
authors.forename: Shouhei
authors.initials: S
authors.lastname: Noshiro
authors.affiliation: Department of Neurosurgery, Sapporo Medical University, School of Medicine, Japan; Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University, School of Medicine, Japan. Electronic address: tmikami@sapmed.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mikami
authors.affiliation: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University, School of Medicine, 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, 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 Public Health, Sapporo Medical University, School of Medicine, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohnishi
authors.affiliation: Department of Neurosurgery, Sapporo Medical University, School of Medicine, Japan; Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University, School of Medicine, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Ohtaki
authors.affiliation: Department of Neurosurgery, Sapporo Medical University, School of Medicine, Japan; Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University, School of Medicine, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Wanibuchi
authors.affiliation: Department of Neurosurgery, Sapporo Medical University, School of Medicine, 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, 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; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D005260:Female; D020786:Hemangioma, Cavernous, Central Nervous System / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; D013925:Thromboplastin
keywords: Cerebral cavernous malformations; Endothelial cell; Tissue factor