Co-expression of tissue factor and IL-6 in immature endothelial cells of cerebral cavernous malformations

J Clin Neurosci. 2017 Mar:37:83-90. doi: 10.1016/j.jocn.2016.12.023. Epub 2017 Jan 10.

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.

Keywords: Cerebral cavernous malformations; Endothelial cell; Tissue factor.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / metabolism
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Child
  • Child, Preschool
  • Endothelial Progenitor Cells / metabolism*
  • Female
  • Hemangioma, Cavernous, Central Nervous System / metabolism*
  • Hemangioma, Cavernous, Central Nervous System / pathology
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Thromboplastin / genetics
  • Thromboplastin / metabolism*

Substances

  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • RNA, Messenger
  • Thromboplastin