Angiogenesis, vascular endothelial growth factor and its receptors in human surgical wounds

Angiogenesis plays an essential role in tissue repair. Vascular endothelial growth factor (VEGF) mediates angiogenesis through receptor kinases VEGF-R1 and VEGF-R2, and co-receptors, neuropilins Np1 and Np2. This study examined the spatial and temporal expression of these factors in relation to angiogenesis in surgical wounds.

Scar biopsies were obtained from patients between 3 days and 2 years after surgery. Normal skin control biopsies were taken during surgery. Microvessel density (MVD) was quantified using a Chalkley grid. VEGF, VEGF-R1, VEGF-R2, Np1 and Np2 endothelial expression was determined by immunohistochemistry, and correlated with MVD and scar age.

Cumulative MVD was significantly greater in scars than controls (P = 0.011), and was related to scar age (P = 0.007). Expression of VEGF, VEGF-R2, Np1 and Np2 was increased significantly in all scars and correlated with MVD. In contrast, scar VEGF-R1 expression was decreased, and correlated with increased VEGF and VEGF-R2.

Levels of VEGF, VEGF-R2, Np1 and Np2 are increased, whereas VEGF-R1 expression is decreased in angiogenesis, suggesting a role for VEGF-receptor complexes in early wound healing. This altered protein expression and increased presence of vessels is prolonged, suggesting that structural remodelling continues for at least 2 years after surgery.