Redefined role of angiogenesis in the pathogenesis of dural arteriovenous malformations

Abstract

To investigate the role of angiogenesis in the pathogenesis of dural arteriovenous malformations (AVMs), 40 rats underwent common carotid artery-external jugular vein (CCA-EJV) anastomosis, bipolar coagulation of the vein draining the transverse sinus, and sagittal sinus thrombosis to induce venous hypertension. Fifteen rats underwent a similar surgical procedure, but venous hypertension was not induced. The 55 rats were divided into seven groups. Four groups, each containing 10 rats, underwent induced venous hypertension. The other three groups, each containing five rats, did not undergo induced venous hypertension. After 1, 2, or 3 weeks, dura mater was obtained from one group of hypertensive rats and from one group of nonhypertensive rats and was assayed for angiogenic activity (rabbit cornea bioassay). The remaining group of 10 hypertensive rats was not assayed to determine if sampling affected dural AVM formation. Unlike rats without CCA-EJV anastomosis, rats with CCA-EJV anastomosis had significantly increased postoperative sagittal sinus pressures (p < 0.0001). Mean angiogenesis indices were significantly greater in rats with venous hypertension than in rats without venous hypertension (p = 0.004). Dural AVMs formed in 42% of the 55 rats and facial AVMs formed in 51%. Angiogenic activity correlated positively with venous hypertension (p = 0.74). Development of dural AVMs correlated positively with both venous hypertension (p = 0.0009) and angiogenic activity (p = 0.04). These data indicate that venous hypertension may induce angiogenic activity either directly or indirectly by decreasing cerebral perfusion and increasing ischemia, and that dural AVM formation may be the result of aberrant angiogenesis.