PB0343 - Localized recombinant human von Willebrand Factor influences in vivo angiogenesis in VWF‐deficient mice

Background: Repeated bleeding from Gastrointestinal (GI) angiodysplasia (mucosal and submucosal vascular malformations) is a clinical challenge in patients with severe von Willebrand disease (VWD). The condition is often refractory to standard treatment including von Willebrand Factor (VWF) replacement therapy, with patients requiring repeated red cell transfusions and hospitalizations. The established inhibitory effect of VWF on angiogenesis supports the hypothesis that VWF abnormalities contribute to the underlying mechanisms of angiodysplasia development.

Aims: To evaluate the effect of localized VWF on in vivo angiogenesis in a VWF‐deficient mouse model.

Methods: 10 to 12-week C57Bl/6 VWF-/- mice of both sexes were used (N=15). Matrigel mixed with recombinant fibroblast growth factor (FGF) basic (146 aa), recombinant human vascular endothelial growth factor (VEGF165) and recombinant human VWF (rhVWF, VONVENDI®) at 10 IU/ml was injected subcutaneously in the right back flank of mice (experimental). Similar injections without rhVWF were made in the left back flank (controls). After seven days, plugs were excised and processed for hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining.

Results: Compared to the experimental plugs, controls were dark red, indicating the presence of erythrocytes. These control plugs showed increased capillary formation and red cells on H&E compared to experimental plugs that showed fewer capillaries. A similar pattern was observed on IHC staining as evidenced by higher signals of CD31, which stains murine endothelial cells, in control plugs. (Figure 1). NG2 staining for pericytes was significantly raised in control plugs, with ASMA staining for smooth muscle cells showing a similar trend (Figure 1B).

Conclusion(s): The addition of rhVWF to plugs reduced vessel formation and likely influenced vessel maturity as evidenced by the difference in pericyte staining of plug sections with or without rhVWF. Understanding the role of VWF in angiogenesis could reveal new therapeutic targets, leading to improved patient management strategies.