Expression of angiogenic growth factors in dural arteriovenous fistula

Abstract

Object. Although various mechanisms of the development of dural arteriovenous fistula (AVF) have been described, the exact course of its pathogenesis, including molecular processes mediating its genesis, is still unknown. Recently, the importance of sinus thrombosis and venous hypertension has been reported in experimental and clinical studies. Additionally, a role of angiogenic growth factors in the pathogenesis of vascular malformations of the central nervous system has been reported. In this study, the authors investigated the existence of sinus thrombosis in dural AVF and the expression of angiogenic growth factors (basic fibroblast growth factor [bFGF] and vascular endothelial growth factor [VEGF]) in nine patients with dural AVFs that were surgically resected.Methods. The authors examined histological features of dural AVFs that involved the transverse/sigmoid sinus in seven patients and the superior sagittal sinus in two. Sinus thrombosis was verified angiographically in seven cases and histologically in all cases. In surgically resected specimens the angiogenic growth factors bFGF and VEGF were examined immunohistochemically in nine patients with dural AVFs, with five dural sinuses from cadavers with unrelated central nervous system diseases serving as a normal control group. The media and perivascular connective tissues of the arteries in the wall of the normal dural sinuses stained faintly for bFGF; on the other hand, the expression of VEGF was not detected. In all patients with dural AVFs, the thick wall of the dural sinus stained strongly for bFGF, mainly in the subendothelial layer and media of the strongly proliferative vessels in the sinus wall, in addition to the perivascular connective tissues. In all nine cases VEGF was expressed in the endothelium of the sinus and perivascular connective tissues. In two cases, VEGF was expressed in many capillaries proliferating in the granulation-like tissues in sinuses that were obliterated by organized thrombi.Conclusions. It is concluded that the pathogenesis of dural AVF is still unknown, but that angiogenic growth factors, which might be produced by the healing process due to sinus thrombosis, may participate in the genesis of dural AVF. Understanding the mechanism of molecular pathogenesis in the development of dural AVF might aid in the establishment of a new therapeutic strategy for this dynamic vascular disease.