title: Angiogenic response pattern during normal and impaired skin flap re-integration in mice: a comparative study.
abstract: BACKGROUND
  Distal 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.
  
  
  METHODS
  Histologic, qRT-PCR, ELISA and immunoblot techniques determined expression and localization of angiogenesis-related growth factors, receptors and cell types upon skin flap re-integration.
  
  
  RESULTS
  Skin 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.
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: pharmazentrum frankfurt/ZAFES (Head: Prof. M. D. Josef Pfeilschifter), Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. Electronic address: Schuermann@med.uni-frankfurt.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schürmann
authors.affiliation: pharmazentrum frankfurt/ZAFES (Head: Prof. M. D. Josef Pfeilschifter), Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Schmidt
authors.affiliation: pharmazentrum frankfurt/ZAFES (Head: Prof. M. D. Josef Pfeilschifter), Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany; Klinik für Mund-, Kiefer- und Plastische Gesichtschirurgie (Head: Prof. Robert Sader), Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Seitz
authors.affiliation: pharmazentrum frankfurt/ZAFES (Head: Prof. M. D. Josef Pfeilschifter), Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Pfeilschifter
authors.affiliation: pharmazentrum frankfurt/ZAFES (Head: Prof. M. D. Josef Pfeilschifter), Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Frank
mesh_terms: D000818:Animals; D062109:Dermatologic Surgical Procedures / Q000379:methods; D003920:Diabetes Mellitus / Q000473:pathology / Q000503:physiopathology*; D004848:Epithelium / Q000473:pathology; D005260:Female; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000032:analysis; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D015603:Keratinocytes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D055806:Microvessels / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D042787:Receptor, TIE-2 / Q000032:analysis; D050800:STAT6 Transcription Factor / Q000032:analysis; D012867:Skin / Q000098:blood supply* / Q000473:pathology; D013524:Surgical Flaps / Q000098:blood supply* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis; D014945:Wound Healing / Q000502:physiology
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); C501163:Flt1 protein, mouse; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Angiogenesis; Diabetes mellitus; HIF-1α; Surgical flaps; VEGF; Wound healing