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. 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 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.
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. 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 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: Maximilian Ackermann; Tanja Wolloscheck; Axel Wellmann; Vincent W Li; William W Li; Moritz A Konerding Journal: Int J Mol Med Date: 2011-03-03 Impact factor: 4.101
Authors: Jillian E Tengood; Ryan Ridenour; Ross Brodsky; Alan J Russell; Steven R Little Journal: Tissue Eng Part A Date: 2011-01-17 Impact factor: 3.845
Authors: Millicent Ford Rauch; Sara Royce Hynes; James Bertram; Andy Redmond; Rebecca Robinson; Cicely Williams; Hao Xu; Joseph A Madri; Erin B Lavik Journal: Eur J Neurosci Date: 2009-01 Impact factor: 3.386
Authors: Susan Ormonde; Chi-Ying Chou; Lucy Goold; Con Petsoglou; Rasha Al-Taie; Trevor Sherwin; Charles N J McGhee; Colin R Green Journal: J Membr Biol Date: 2012-07-15 Impact factor: 1.843
Authors: Mariana Barreto Serra; Wermerson Assunção Barroso; Neemias Neves da Silva; Selma do Nascimento Silva; Antonio Carlos Romão Borges; Iracelle Carvalho Abreu; Marilene Oliveira da Rocha Borges Journal: Int J Inflam Date: 2017-07-25