title: Exogenous pro-angiogenic stimuli cannot prevent physiologic vessel regression.
abstract: BACKGROUND
  In healing wounds, rising levels of vascular endothelial growth factor (VEGF) induce a period of robust angiogenesis. The levels of pro-angiogenic factors in the wound begin to decline just before a period of vascular regression, suggesting that these mediators are necessary to sustain vessel density. The purpose of this study was to determine if the maintenance of pro-angiogenic stimuli in the wound would prevent physiological vessel regression.
  
  
  METHODS
  A standard subcutaneous sponge wound model was modified by the addition of a mini-osmotic pump, allowing manipulation of the wound milieu by the addition of exogenous growth factors. After initial characterization of this model, exogenous VEGF (10 microg/mL), FGF (10 microg/mL), PDGF (10 microg/mL), or VEGF (10 microg/mL) plus FGF (10 microg/mL) were delivered to wounds and blood vessel density analyzed by immunohistochemistry.
  
  
  RESULTS
  VEGF administration resulted in a transient increase in wound vessel density (P < 0.05). None of the pro-angiogenic growth factors (VEGF, FGF, PDGF, VEGF/FGF) were able to prevent vascular regression (P = NS).
  
  
  CONCLUSIONS
  These findings suggest that the anti-angiogenic signals that mediate physiological vascular regression in wounds are strongly dominant over pro-angiogenic stimuli during the later phases of wound healing. Clinical manipulation of anti-angiogenic signals in addition to the currently used pro-angiogenic targets may be needed to achieve therapeutic modulation of blood vessel density.
authors.affiliation: Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Burn and Shock Trauma Institute, Maywood, Illinois, USA.
authors.forename: Ankush
authors.initials: A
authors.lastname: Gosain
authors.forename: Annette M
authors.initials: AM
authors.lastname: Matthies
authors.forename: Julia V
authors.initials: JV
authors.lastname: Dovi
authors.forename: Adrian
authors.initials: A
authors.lastname: Barbul
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gamelli
authors.forename: Luisa A
authors.initials: LA
authors.lastname: DiPietro
mesh_terms: D000704:Analysis of Variance; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000254:growth & development; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D043925:Angiogenesis Inducing Agents; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D005346:Fibroblast Growth Factors