Angiogenic response pattern during normal and impaired skin flap re-integration in mice: A comparative study

Abstract

BackgroundDistal skin flap necrosis represents a severe complication in surgery. This study investigated angiogenic responses in healthy and impaired pedicled skin flap tissue in normal and diabetic mice. MethodsHistologic, qRT-PCR, ELISA and immunoblot techniques determined expression and localization of angiogenesis-related growth factors, receptors and cell types upon skin flap re-integration. ResultsSkin flap tissue re-integration was severely disturbed in diabetic mice. Impaired skin flap tissue lost early VEGF expression from wound margin keratinocytes and markedly reduced expression of endothelium-specific receptors Tie-2 and FLT-1. Numbers of blood vessels were reduced in impaired flaps. In addition, HIF-1α protein was absent from disturbed skin flap tissue. Reduced VEGF expression and the loss of epithelium in disturbed skin flaps were paralleled by the appearance of VEGF expressing inflammatory infiltrate. ConclusionIn summary, our data show a dysregulated spatial and temporal pattern of angiogenic processes during skin flap re-integration in diabetic mice. Our data suggest that reduced expression of angiogenic receptors in skin flap tissue might contribute to a loss of VEGF function in impaired tissue.