VEGF and AVM: Translational Research in Action

Introduction Arteriovenous malformations (AVMs) are regarded rare diseases and are prone to complications such as pain, bleeding, relentless growth and high volume of shunted blood. Endothelial cells are exposed to mechanical stress due to high vascular pressure. New medical treatment strategies are needed to downsize unresectable lesions prior to surgery or treat them systemically.

Methods AVM cells were isolated from three patients and exposed to cyclic mechanical stretching for 24 hours. Thalidomide and bevacizumab, both VEGF inhibitors, were tested in their ability to prevent tube formation and proliferation of AVM cells. Furthermore, the effect of Thalidomide and bevacizumab on stretched AVM cells was evaluated. With promising in vitro results, bevacizumab was used to treat a 25-year-old female patient with an unresectable AVM of the right face.

Results In response to mechanical stress VEGF gene and protein expression increased in patient AVM cells. Thalidomide and bevacizumab were able to reduce AVM cell proliferation. Bevacizumab inhibited tube formation of AVM cells and lowered VEGF gene and protein expression, even though the cells were exposed to mechanical stress. In addition, bevacizumab was able to control bleeding, pulsation and pain in the treatment of an AVM patient over the follow up period of 8 months with no side effects.

Conclusions Mechanical stress increases VEGF expression in AVM cells. Bevacizumab, a monoclonal VEGF antibody, is able to alleviate this effect, prevent tube formation and proliferation of AVM cells in vitro. The clinical application of these results showed an effective symptom control with no side effects with bevacizumab treatment of an AVM patient.

Publication History

Article published online:
12 May 2023