Abstract 2585: Capillary Rarefaction Might Explain Arterial Hypertension in Patients Receiving Bevacizumab
Background: The anti-angiogenic agent bevacizumab (Avastin®) has been rationally designed to target vascular endothelial growth factor (VEGF), a key mediator of tumor angiogenesis. Arterial hypertension (HT) has been reported in all studies involving bevacizumab. The mechanism underlying bevacizumab-related HT is not yet clearly understood and recent studies have demonstrated that humoral factors involving the renin-angiotensin system, endothelin, and the sympathetic nervous system had little role in the observed increase in BP.
Objective: As far as microvascular rarefaction has been reported in all forms of human and experimental HT, we tested the hypothesis that anti VEGF therapy could induce microvascular rarefaction in non-tumoral tissues and, thus, result in an increase in BP.
Patients & methods: We used intravital video-microscopy to measure basal and maximal (during venous congestion) skin capillary densities in the dorsum of the fingers. Microvascular endothelial function was assessed by laser-Doppler flowmetry combined with iontophoresis of three cumulative doses of acetylcholine (ACh). All measurements were performed in 16 patients (mean±SD: 59±10 year old) before and after a 6 months treatment with bevacizumab (mean cumulative dose: 3.16±0.90 g).
Results: are summarized in the following table⇓ (mean±SD):
Conclusion: Pharmacological blockage of VEGF receptors results in endothelial dysfunction and capillary rarefaction in humans. Both changes are closely associated and could be responsible for the rise in blood pressure observed in patients receiving this treatment.