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 proangiogenic 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. Materials and 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 mu g/mL), FGF (10 mu g/mL), PDGF (10 mu g/mL), or VEGF (10 mu g/mL) plus FGF (10 mu g/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 antiangiogenic 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. (c) 2006 Elsevier Inc. All rights reserved.