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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kumar
I
I
Academic Unit of Surgical Oncology, University of Sheffield Medical School, Sheffield, UK.
Staton
C A
CA
Cross
S S
SS
Reed
M W R
MW
Brown
N J
NJ
D001941:Breast Diseases / Q000378:metabolism / Q000473:pathology; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008833:Microcirculation / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D039921:Neuropilins / Q000378:metabolism; D015588:Observer Variation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
D039921:Neuropilins; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2