Expression of thioredoxin-1 and hypoxia inducible factor-1α in cerebral arteriovenous malformations: Possible role of redox regulatory factor in neoangiogenic property

BACKGROUND: Recently it is reported that proliferative activity remains in vascular walls of cerebral arteriovenous malformations (AVMs). These reports indicate that endothelial cells in AVMs have the neoangiogenic property. In this study, we assess the role of thioredoxin-1 (Trx-1) and hypoxia-inducible factor 1a (HIF-1α) in AVMs. These factors are reported to play a role in neoangiogenesis. METHODS: We analyzed the expressions of Trx1 in the specimens of human cerebral AVMs. In addition, we also analyzed the expression of HIF-1α in these specimens by immunohistochemical method and RT-PCR. Furthermore, we assessed the effect of redox state and expression of Trx-1 during neoangiogenesis using in vitro angiogenesis assay. FINDINGS: Trx-1 and HIF-1α immunoreactivity was detected in almost all 17 specimens of AVMs. Trx-1 and HIF-1α immunoreactive cells were distributed mainly endothelium of intranidal arteries and enlarged veins with thickened vascular walls. Double staining shows that Trx-1 and VEGF (vascular endothelial growth factor) immunoreactivity were colocalized in the same cells. These cells were considered to be endothelial cells. HIF-1α immunoreactivity was also colocalized with VEGF immunoreactivity in endothelium. As for influencing factors, the presence of deep drainers and convulsion significantly associated with HIF-1α expression. Trx-1 assessed by western blotting decreased at 6 hours and 12 hours after plating on Matrigel, which is a model of angiogenesis. CONCLUSIONS: We have shown that the endothelial induction of Trx-1 and HIF-1α in cerebral AVMs. Based on all findings obtained in this study, Trx-1 may affect the neoangiogenic property of cerebral AVMs.