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Biological relevance of tissue factor and IL-6 in arteriovenous malformations

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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.

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Authors and Affiliations

  1. Department of Neurosurgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan

    Shouhei Noshiro, Takeshi Mikami, Shunya Ohtaki, Masahiko Wanibuchi & Nobuhiro Mikuni

  2. Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan

    Shouhei Noshiro, Takeshi Mikami, Yuko Kataoka-Sasaki, Masanori Sasaki, Kazuo Hashi, Shunya Ohtaki, Masahiko Wanibuchi & Osamu Honmou

  3. Department of Neurology, Yale University School of Medicine, New Haven, CT, 06510, USA

    Masanori Sasaki, Jeffery D. Kocsis & Osamu Honmou

  4. Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT, 06516, USA

    Masanori Sasaki, Jeffery D. Kocsis & Osamu Honmou

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  1. Shouhei Noshiro
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  2. Takeshi Mikami
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Correspondence to Takeshi Mikami.

Ethics declarations

This work was supported in part by JSPS KAKENHI grant number 25462226 (to O.H.) as well as the RR&D Service of Department of Veterans Affairs (B7335R, B9260L), the NMSS [RG2135], and the CT Stem Cell Research Program (12-SCB-Yale-05).

The study protocol was approved by the ethics committee of Sapporo Medical University Hospital, and all subjects signed informed consent.

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The authors declare that they have no conflict of interest.

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Noshiro, S., Mikami, T., Kataoka-Sasaki, Y. et al. Biological relevance of tissue factor and IL-6 in arteriovenous malformations. Neurosurg Rev 40, 359–367 (2017). https://doi.org/10.1007/s10143-016-0780-1

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  • DOI: https://doi.org/10.1007/s10143-016-0780-1

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