Plasma vascular endothelial growth factor and serum soluble angiopoietin receptor sTIE-2 in patients with dural arteriovenous fistulas: a pilot study

Abstract

Our aim was to correlate concentrations of circulating vascular endothelial growth factor (VEGF) and serum soluble angiopoietin receptor (sTIE-2) before and after endovascular treatment with the grading in human dural arteriovenous fistulas (DAVFs). In ten patients with DAVFs undergoing diagnostic cerebral angiography and endovascular intervention, pre-treatment and post-treatment levels of plasma VEGF and serum TIE-2 were examined in a prospective study design. A total of 32 plasma samples and 19 serum samples was collected from the cubital vein, the arterial sheath before and--if applicable--after intervention. Plasma VEGF and serum Tie-2 levels were measured by standardized ELISA protocols. In eight of ten patients with DAVF increased circulating VEGF levels (elevation of more than mean + 2 SD of published normal values) were found, whereas two patients showed increased sTIE-2 levels. Six of the seven patients treated by endovascular embolization displayed a post-interventional decrease of VEGF values. The serum TIE-2 levels decreased slightly after intervention. Pre-treatment vVEGF levels varied significantly between patients with grades I and II/III fistulas according to the Cognards classification system. Our pilot study suggests that assessment of angiogenesis parameters in patients with DAVFs might correlate with the DAVFs' grade. To support the hypothesis that a change in angiogenic indicators may serve as indicators for a response to therapy, a larger number of patients should be followed for a longer time period.

Plasma Levels of Vascular Endothelial Growth Factor After Treatment for Cerebral Arteriovenous Malformations

“…27,45 Similarly, Klisch et al found plasma VEGF levels in patients with dural arteriovenous fistulas to decrease following endovascular treatment. 21 Another possible explanation for our findings is the presence of an AVM "sink" in which circulating VEGF is trapped by the AVM, thereby leading to low systemic levels and high local levels of VEGF. After AVM resection, systemic VEGF levels normalize over time secondary to removal of the source of VEGF sequestration.…”

“…12 A recent study reported a significant increase in circulating VEGF levels in AVM patients compared to healthy controls. 40 Increased expression of circulating VEGF has also been associated with other cerebrovascular disorders including intracranial aneurysms, 41 dural arteriovenous fistulas, 21 and vasospasm after subarachnoid hemorrhage. 5 VEGF expression is regulated by numerous factors, most significantly hypoxia.…”

Hypothetical Mechanism of the Formation of Dural Arteriovenous Fistula – The Role and Course of Thrombosis of Emissary Vein and Sinuses

“…Extracranial arteries on the skull or under the skull base are often mobilized through the bone. Such active recruitment of feeders is considered to be due to angiogenesis enhanced by the expression of vasculogenetic factors at the affected dura (including vascular endothelial growth factor (VEGF)) [11][12][13][14][15][16] . The next key process in maturation of the DAVF is the occlusive change of the draining system.…”

“…This occlusive process is typical in the DAVF at CS 17 . Its drainage route gradually occludes from the inferior petrosal sinus and superior ophthalmic vein 11 , and occasionally causes a paradoxical worsening of visual acuity and chemosis with ocular hypertension following occlusion of the anterior drainage route. During this progression, the thrombophilic abnormalities characteristic of DAVF are also reported [18][19][20][21][22] .…”

The use of vascular biomarkers and imaging studies in the early clinical development of anti‐tumour agents targeting angiogenesis

“…In conditioned media of phorbol myristate acetate (PMA)-stimulated endothelial cells, a soluble form of this receptor comprising parts of the extracellular domain can be detected. Finally, the soluble form of TIE-2 can also be detected in human biological fluids such as sera and plasma from healthy controls [17]. The complete set of the above-mentioned plasma and serum biomarkers were evaluated to assess the biological activity of PTK787/ZK 222584 (PTK/ZK), an angiogenesis inhibitor targeting all known VEGF receptor tyrosine kinases.…”