4.3 Article

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

Journal

JOURNAL OF CLINICAL NEUROSCIENCE
Volume 37, Issue -, Pages 83-90

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.jocn.2016.12.023

Keywords

Cerebral cavernous malformations; Endothelial cell; Tissue factor

Funding

  1. JSPS KAKENHI - JAPAN [25462226]
  2. RR&D Service of Department of Veterans Affairs [B7335R, B9260L]
  3. National Multiple Sclerosis Society United States [RG2135]
  4. CT Stem Cell Research Program [12-SCB-Yale-05]
  5. Grants-in-Aid for Scientific Research [25462226] Funding Source: KAKEN

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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, rho = 0.62). The mRNA expression level of IL-6 was significantly correlated with the mRNA expression level of TF (p = 0.034, rho = 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+/1L-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. (C) 2016 Elsevier Ltd. All rights reserved.

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