Vascular endothelial growth factor expression in expanded tissue: a possible mechanism of angiogenesis in tissue expansion.

Vascular endothelial growth factor (VEGF) is a major angiogenic growth factor. Angiogenesis stimulated by VEGF occurs in several important clinical contexts, including myocardial ischemia, retinal disease, and tumor growth. The level of VEGF is increased in several skin disorders and is stimulated by ischemia. Tissue expansion has been shown to induce angiogenesis and ischemia on the overlying skin. We therefore investigated the hypothesis that VEGF was expressed in expanded tissue. Three samples of skin were obtained from five patients who sustained reconstruction with tissue expansion. One sample was taken on the implantation site of the expander before implantation. Two samples were taken at the time of removal, respectively, one on the nonexpanded skin adjacent to the expanded area and one on the expanded skin on the site of expansion. On these samples we performed immunolocalization of VEGF. Mouse monoclonal antibody was used, recognized with rabbit anti-mouse immunoglobulin alkaline phosphatase-anti-alkaline phosphatase (APAAP) complex conjugated and revealed with naphthol red. Our results showed clearly an increased number of cells that fixated VEGF antibody on the site of expansion. Cell counts revealed that the numbers of cells expressing VEGF were statistically higher in expanded tissue than in nonexpanded tissue. Before expansion skin specimens did not express VEGF. These findings are the first to show the presence of a growth factor in expanded tissue. They open a new field of research on the biological explanation of tissue-expanded angiogenesis.