Intranasal submucosal application of Bevacizumab in hereditary hemorrhagic telangiectasia (HHT) – the effect on endothelial cell proliferation and VEGF expression – an in vitro study

Background and Objectives Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia with recurrent epistaxis as the most frequent manifestation. As the proangiogenic factor vascular endothelial growth factor (VEGF) is significantly higher in HHT patients, the use of bevacizumab as a current therapeutic approach seems promising. The purpose of this study was to determine the toxicity and efficacy of Bevacizumab by analysing its effect on cell proliferation and VEGF concentration.

Patients and Methods In this in vitro study, human vascular endothelial cells of HHT patients and healthy controls were incubated with different concentrations of Bevacizumab (2, 4, 6, 8, 10 mg/ml). After 24, 48 and 72 hours, cell proliferation was measured as well as the VEGF concentration in the supernatant of all cells.

Results After an initial decrease of proliferation in all cells, those incubated with Bevacizumab concentrations of up to 4 mg/ml recovered within 72 hours whereas those with higher concentrations of 6, 8 and 10 mg/ml had a continuous decline in their cell proliferation. Cells incubated with lower Bevacizumab concentrations had initially after 24h a decline in the VEGF concentration which then increased again after 48 and 72h.

Conclusions This study suggests that the intranasal submucosal application of Bevacizumab should not exceed the concentration of 4 mg/ml as higher concentrations seem to have a more toxic effect and jeopardize cell proliferation as well as VEGF concentration.

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Publication History

Article published online:
10 June 2020