Expression and Activation of STAT Family Proteins in Cerebral Arteriovenous Malformations

ObjectiveCerebral arteriovenous malformations (AVMs) do not seem to be static congenital vascular malformations but rather are dynamically changing pathologies. In this work, we investigated the expression and possible activation of different signal transducers and activators of transcription (STAT) family members in AVM nidus.MethodsImmunohistochemical analysis was conducted on 25 AVM specimens from 24 patients using antibodies against STATs 1, 3, 5, and 6 as well as their phosphorylated forms. Analysis was also undertaken to determine if there is any correlation between STAT activation and different clinical parameters of AVM patients.ResultsOur studies revealed that both STATs 1 and 3 were highly expressed in cerebral AVM, mainly in the endothelium of AVM blood vessels and perivascular infiltrating inflammatory cells within the nidus. STAT3 showed the most intense level of expression within the endothelium and perivascular infiltrating inflammatory cells. It was intensely expressed in the endothelium of 25 (100%) specimens and in the infiltrating inflammatory cells of 24 (96%) specimens. The expression of the phospho-STATs 1 and 3 was also high in the endothelium and perivascular infiltrating inflammatory cells indicating activation of STATs 1 and 3 in AVM. We could not find any significant effect of hemorrhage or preoperative embolization, or other clinical parameters, on the activation of STATs 1 and 3 in cerebral AVMs.ConclusionWe obtained evidence for significant overexpression and activation of both STATs 1 and 3 in cerebral AVM, thus suggesting an important role for these proteins in mediating the pathophysiology of cerebral AVM.