[Transactivation of the vascular endothelial growth factor receptor KDR/Flk-1 by the bradykinin B2 receptor induces an angiogenic phenotype in human cultured coronary endothelial cells].

BACKGROUND

Endothelial cells (ECs) are believed to be critical cellular elements responsible for postnatal angiogenesis. Vascular endothelial growth factor (VEGF) stimulates angiogenesis via the activation of KDR/Flk-1 receptor, which is mainly expressed in ECs. Transactivation of KDR/Flk-1 receptor by bradykinin (BK) B2 receptor contributes to the activation of endothelial nitric-oxide (NO) synthase. Therefore, we examined whether transactivation by BK induced angiogenesis.

METHODS AND RESULTS

We developed an in vitro model of human coronary artery ECs (HCECs) tube formation on a matrix gel. We demonstrated that BK dose-dependently induced tube formation. Although a lower concentration of BK did not induce tube formation, the combination of a lower concentration of BK and VEGF did. These effects blocked specific inhibitors of VEGF receptor tyrosine kinases (Tki) and NO synthase. In addition, BK induced the tyrosine phosphorylation of KDR/FlK-1 receptor (transactivation), as did VEGF itself. This transactivation was also blocked by Tki.

CONCLUSIONS

Transactivation of KDR/Flk-1 by BK through B2 receptor is a potent signaling in angiogenic phenotype in HCECs.