Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing

Am J Pathol. 1998 Jun;152(6):1445-52.


Angiogenesis is an essential component of normal wound repair, yet the primary mediators of wound angiogenesis have not been well described. The current study characterizes the contribution of vascular endothelial cell growth factor (VEGF) to the angiogenic environment of human surgical wounds. Surgical wound fluid samples (n = 70) were collected daily for up to 7 postoperative days (POD) from 14 patients undergoing mastectomy or neck dissection. VEGF levels in surgical wound fluid were lowest on POD 0, approximating values of serum, but increased steadily through POD 7. An opposite pattern was noted for basic fibroblast growth factor-2. Fibroblast growth factor-2, which has been previously described as a wound angiogenic factor, exhibited highest levels at POD 0, declining to near serum levels by POD 3. Surgical wound fluid form all time points stimulated marked endothelial cell chemotaxis and induced a brisk neovascular response in the rat corneal micropocket angiogenesis assay. Antibody neutralization of VEGF did not affect the in vitro chemotactic or the in vivo angiogenic activity early wound samples (POD 0). In contrast, VEGF neutralization significantly attenuated both chemotactic activity (mean decrease 76 +/- 13%, P < 0.01) and angiogenic activity (5 of 5 samples affected) of later wound samples (POD 3 and 6). The results suggest a model of wound angiogenesis in which an initial angiogenic stimulus is supplied by fibroblast growth factor-2, followed by a subsequent and more prolonged angiogenic stimulus mediated by VEGF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Animals
  • Antibodies / pharmacology
  • Cells, Cultured
  • Endothelial Growth Factors / analysis
  • Endothelial Growth Factors / immunology
  • Endothelial Growth Factors / metabolism
  • Endothelial Growth Factors / physiology*
  • Endothelium / drug effects
  • Endothelium / physiology
  • Exudates and Transudates / chemistry*
  • Female
  • Fibroblast Growth Factor 2 / analysis
  • Fibroblasts / metabolism
  • Humans
  • Immunohistochemistry
  • Lymphokines / analysis
  • Lymphokines / immunology
  • Lymphokines / metabolism
  • Lymphokines / physiology*
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology*
  • Rats
  • Time Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Wound Healing / physiology*


  • Antibodies
  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Fibroblast Growth Factor 2