Exogenous Pro-Angiogenic Stimuli Cannot Prevent Physiologic Vessel Regression

Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Burn and Shock Trauma Institute, Maywood, Illinois, USA.
Journal of Surgical Research (Impact Factor: 1.94). 10/2006; 135(2):218-25. DOI: 10.1016/j.jss.2006.04.006
Source: PubMed


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.
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.
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).
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.

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    • "In our previous work, we noted that coculture of NPCs with BECs leds to greater expression of VEGF [19] and we see that here which may play a role in the early protection of the BECs. As a part of this work, we have also looked at the concentration of secreted PDGF-BB, Ang1, and Ang2, factors that are known to be important in vessel stabilization [71]–[73]. We did not see significant differences in the concentration of these secreted factors between the groups, but these are only a few of a large number of factors which can now be screened and tested in this system. "
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