Exogenous pro-angiogenic stimuli cannot prevent physiologic vessel regression.
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.
Gosain
Ankush
A
Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Burn and Shock Trauma Institute, Maywood, Illinois, USA.
Matthies
Annette M
AM
Dovi
Julia V
JV
Barbul
Adrian
A
Gamelli
Richard L
RL
DiPietro
Luisa A
LA
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*
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