Vascular Endothelial Growth Factor Plasma Levels Are Significantly Elevated in Patients with Cerebral Arteriovenous Malformations

Abstract

Background: Since growth and de novo generation of cerebrovascular malformations were demonstrated, a strictly congenital model cannot be further supported as unique factor in the pathogenesis of cerebral arteriovenous malformations (AVMs). Vascular endothelial growth factor (VEGF) has previously been demonstrated to be highly expressed in AVMs by immunohistochemical methods. However, systemic VEGF levels have not been analysed previously. This study aimed to investigate VEGF plasma concentrations as a possible plasma marker for neovascularization in patients with cerebral AVMs compared to healthy controls. Methods: The study included 17 patients with cerebral AVMs and 40 healthy controls. VEGF plasma concentrations were measured by a specific enzyme immuno-assay. Results: VEGF plasma concentrations were significantly higher in patients with cerebral AVMs (mean 140.9 pg/ml, SD 148.5 pg/ml and median 63.0 pg/ml) compared to a healthy control group (mean 44.7 pg/ml, SD 36.4 pg/ml and median 35.0 pg/ml), p = 0.0003. Conclusions: Our findings suggest that VEGF plasma concentrations might play a role in the pathogenesis of cerebral AVMs. Further studies are necessary and would contribute to an improved understanding of the pathogenesis of cerebral AVMs.

De Novo Cerebral Arteriovenous Malformation: Case Report and Literature Review

“…One study demonstrated significantly higher levels of VEGF in patients with AVMs compared with a control group. 13 Patients with hereditary hemorrhagic telangiectasia (HHT) have an increased prevalence of AVMs and also have elevated levels of VEGF. 14,15 Hypoxia is known to stimulate expression of VEGF.…”

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

“…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.…”

“…14,15,20,22 More recently, one study reported significantly elevated circulating VEGF levels in AVM patients compared to healthy controls. 40 VEGF is a dimeric heparin-binding glycoprotein and mediates angiogenesis under both physiological and pathological conditions. 31 It is a highly specific and potent mitogen of vascular endothelial cells, promotes endothelial cell survival and migration, and increases microvascular permeability.…”

De Novo Arteriovenous Malformation in a 4 Year-Old Boy with Headache, with No Previous Cerebrovascular Disease

“…Importantly, these AVMs only occurred after stimulation with vascular endothelial growth factor (VEGF) [28]. Indeed, VEGF promotes vascular proliferation and is markedly increased in patients with cerebral AVM [29]. However, VEGF stimulation alone has never been shown to induce de novo AVM formation in animal models.…”