Discordant effects of a soluble VEGF receptor on wound healing and angiogenesis

Johannes Jacobi, Betty Y.Y. Tam, Uma Sundram, Georges von Degenfeld, Helen M. Blau, Calvin J. Kuo, John P. Cooke

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Soluble receptors to vascular endothelial growth factor (VEGF) can inhibit its angiogenic effect. Since angiogenesis is involved in wound repair, we hypothesized that adenovirus-mediated gene transfer of a soluble form of VEGF receptor 2 (Flk-1) would attenuate wound healing in mice. C57BI/6J and genetically diabetic (db/db) mice (each n=20) received intravenous (i.v.) injections of recombinant adeno-viruses (109 PFU) encoding the ligand-binding ectodomain of VEGF receptor 2 (Flk-1) or cDNA encoding the murine IgG2α Fc fragment (each n=10). At 4 days after gene transfer, two full-thickness skin wounds (0.8cm) were created on the dorsum of each animal. Wound closure was measured over 9-14 days after which wounds were resected for histological analysis. Prior to killing, fluorescent microspheres were systemically injected for quantitation of wound vascularity. Single i. v. injections of adenoviruses encoding soluble Flk-1 significantly decreased wound angiogenesis in both wild-type and diabetic mice. Fluorescence microscopy revealed a 2.0-fold (wild type) and 2.9-fold (diabetic) reduction in wound vascularity in Flk-1-treated animals (p < 0. 05). Impairment of angiogenesis was confirmed by CD31 immunohistochemistry, Interestingly, despite significant reductions in wound vascularity, wound closure was not grossly delayed. Our data indicates that while VEGF function is essential for optimal wound angiogenesis, it is not required for wound closure.

Original languageEnglish (US)
Pages (from-to)302-309
Number of pages8
JournalGene Therapy
Volume11
Issue number3
DOIs
StatePublished - Feb 2004

Keywords

  • Angiogenesis
  • Flk-1
  • Soluble receptor
  • Wound healing

ASJC Scopus subject areas

  • Genetics

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