Expression of angiogenic growth factors in dural arteriovenous fistula

Object. Although various mechanisms of the development of dural arterioveno us fistula (AVF) have been de scribed, the exact course of its pathogenesis , including molecular processes mediating its genesis, is still unknown. Re cently, the importance of sinus thrombosis and venous hypertension has been reported in experimental and clinical studies. Additionally, a role of ang iogenic growth factors in the pathogenesis of vascular malformations of the central nervous system has been reported. In this study, the authors inves tigated the existence of sinus thrombosis in dural AVF and the expression o f angiogenic growth factors (basic fibroblast growth factor [bFGF] and vasc ular endothelial growth factor [VEGF]) in nine patients with dural AVFs tha t were surgically resected. Methods. The authors examined histological features of dural AVFs that invo lved the transverse/sigmoid sinus in seven patients and the superior sagitt al sinus in two. Sinus thrombosis was verified angiographically in seven ca ses and histologically in all cases. In surgically resected specimens the a ngiogenic growth factors bFGF and VEGF were examined immunohistochemically in nine patients with dural AVFs, with five dural sinuses from cadavers wit h unrelated central nervous system diseases serving as a normal control gro up. The media and perivascular connective tissues of the arteries in the wa ll 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 nin e cases VEGF was expressed in the endothelium of the sinus and perivascular connective tissues. In two cases, VEGF was expressed in many capillaries p roliferating in the granulation-like tissues in sinuses that were obliterat ed by organized thrombi. Conclusions. It is concluded that the pathogenesis of dural AVF is still un known, but that angiogenic growth factors, which mi ht be produced by the h ealing process due to sinus thrombosis, may participate in the genesis of d ural AVF. Understanding the mechanism of molecular pathogenesis in the deve lopment of dural AVF might aid in the establishment of a new therapeutic st rategy fur this dynamic vascular disease.