The effect of vascular endothelial growth factor on the healing of ischaemic skin wounds

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Abstract

The effect of exogenous vascular endothelium growth factor (VEGF) on wound healing in an ischaemic skin flap model was evaluated in this study. Seventy-two Sprague–Dawley rats were used. Normal incisional wound and H-shaped double flaps were used as the wound models. The study was divided into two parts. In Part I, VEGF protein levels were determined from the incisional and H-shaped ischaemic wounds at 12 and 24 h, postoperatively. In Part II, tensile strength and immunohistochemical stains were examined to determine the level of microvessel density (MVD) at 1 and 2 weeks, postoperatively in simple incisional wounds, ischaemic wounds, and ischaemic wounds following 1 ml (1 μg/ml) exogenous VEGF injections into the subcutaneous tissue. The results showed a significantly higher level of VEGF protein in the ischaemic wounds than the incisional wounds. Tensile strength was statistically higher in the incisional wound group and in the ischaemic flap wounds with VEGF treatment compared to the ischaemic flaps with no treatment at 1 week, postoperatively (p>0.05). MVD data indicated that ischaemic wound repair with VEGF treatment had significantly higher MVD than the normal incisional wounds and ischaemic wounds without treatment. We conclude that exogenous application of VEGF can increase early angiogenesis and tensile strength in the ischaemic wound.

Section snippets

Materials and methods

Seventy-two adult male Sprague–Dawley rats weighing between 380 and 420 g were used in the experiment. The National Research Council's guidelines for the care and use of laboratory animals were followed. The rats were anaesthetised using pentobarbital administered by intraperitoneal injection (50 mg/kg). All surgical procedures were performed under sterile conditions. The 165 amino acid isoform of recombinant human VEGF (Genentech Inc., South San Francisco, CA, USA), suspended in

VEGF protein level

The values of VEGF protein from the different wound edges at each time interval are shown in Fig. 3. The VEGF level (mean±SEM) in the simple incision wound was 0.18±0.07 pg/mg tissue weight at 12 h, and slightly increased to 0.26±0.11 pg/mg at 24 h postoperatively. In the ischaemic wound, the VEGF level was 1.04±0.32 pg/mg at 12 h, and significantly increased to 2.43±0.27 pg/mg at 24 h postoperatively. The difference in values between the simple incision wounds and ischaemic wounds was significant (

Discussion

Angiogenesis is a biological mechanism of new capillary formation and involves the activation, migration, and proliferation of endothelial cells from preexisting venules. Angiogenesis can be influenced by many factors including hypoxia, growth factors, matrix components, and metabolic gradients.1., 2. The angiogenic activation of endothelial cells probably plays a role in promoting and regulating other biological events, such as inflammation, fibroblast proliferation, extracellular matrix

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