Bradykinin reduces proliferation and wound healing in primary endothelial cells

Introduction In the context of hereditary angioedema, acute swelling attacks occur due to highly elevated plasma levels of bradykinin. Although the concentration is increased permanently, patients just suffer swelling attacks intermittently. Thus, there must be additional triggers that ultimately lead to these swelling attacks, for example a mechanical damage of the endothelium. The subsequent healing of this could be impaired by bradykinin. This is where our project starts.

Materials and Methods Human Umbilical Vein Endothelial Cells (HUVEC) were incubated with and without bradykinin. The proliferation rate was measured by Real-time Cell Analysis (RTCA), the angiogenesis by tube formation assays. In addition, the influence of bradykinin on the wound healing was analysed by scratch assays. To further investigate a possible cause for a lower proliferation rate, the expression of isotypes and receptors of Vascular Endothelial Growth Factor (VEGF) was measured.

Results The RTCA-measurements revealed a significantly lower proliferation rate in HUVEC after bradykinin incubation then in the control group. The scratch assays indicated a distinctly reduced wound healing in cells after bradykinin incubation compared to the control group. In line with this, a decreased expression of VEGF A and the VEGF-receptor 2 was observed.

Conclusion Bradykinin leads to a significant reduction of the proliferation rate and impaired wound healing. The downregulation of VEGF could be the reason for these observations. This supports the hypothesis that a Bradykinin-mediated wound healing dysfunction as a second hit could be causative for the intermittent appearance of swelling attacks in patients with Bradykinin-mediated angioedema.

Publication History

Article published online:
12 May 2023