The role of vascular endothelial growth factor in wound healing

Abstract

Background: A chronic wound is tissue with an impaired ability to heal. This is often a consequence of one of the following etiologies: diabetes, venous reflux, arterial insufficiency sickle cell disease, steroids, and/or pressure. Healing requires granulation tissue depending on epithelialization and angiogenesis. Currently no growth factor is available to treat patients with impaired healing that stimulates both epithelialization and angiogenesis. The objective is to review is the multiple mechanisms of vascular endothelial growth factor (VEGF) in wound healing.

Materials and methods: The authors reviewed the literature on the structure and function of VEGF, including its use for therapeutic angiogenesis. Particular attention is given to the specific role of VEGF in the angiogenesis cascade, its relationship to other growth factors and cells in a healing wound.

Results: VEGF is released by a variety of cells and stimulates multiple components of the angiogenic cascade. It is up-regulated during the early days of healing, when capillary growth is maximal. Studies have shown the efficacy of VEGF in peripheral and cardiac ischemic vascular disease with minimal adverse effects. Experimental data supports the hypothesis that VEGF stimulates epithelialization and collagen deposition in a wound.

Conclusion: VEGF stimulates wound healing through angiogenesis, but likely promotes collagen deposition and epithelialization as well. Further study of the molecule by utilizing the protein itself, or novel forms of delivery such as gene therapy, will increase its therapeutic possibilities to accelerate closure of a chronic wound.

Figure 1

Demonstration of VEGF’s potential role in a healing wound. By stimulating the endothelial cell, multiple phases of the angiogenic cascade are enhanced. This figure highlights the multiple synergistic stimulants to angiogenesis that may be generated if VEGF is administered to a wound.

Figure 2. VEGF and Cellular Basis of Healing

Note the multiple roles that endogenous cells play in producing VEGF in the local wound environment. Platlets arrive first on Day “0” of wounding, followed by a peak of macrophages at Day 2. Endothelial cells begin to migrate at Day 2 and new capillary endothelium can be seen between Day’s 3–4. By Day 5, new collagen is produced from fibroblasts. The initial cell that releases VEGF are platelets which enter the wound after debridement. In addition, macrophages release VEGF which stimulate endothelial cells to proliferate and migrate. VEGF has been shown to stimulate keratinocyte migration and collagen production via fibroblasts. VEGF secretion also induces release of other growth factors which further stimulate healing.