title: Topical vascular endothelial growth factor reverses delayed wound healing secondary to angiogenesis inhibitor administration.
abstract: The prevention of new blood vessel growth is an increasingly attractive strategy to limit tumor growth. However, it remains unclear whether anti-angiogenesis approaches will impair wound healing, a process thought to be angiogenesis dependent. Results of previous studies differ as to whether angiogenesis inhibitors delay wound healing. We evaluated whether endostatin at tumor-inhibiting doses delayed excisional wound closure. C57/BL6J mice were treated with endostatin or phosphate-buffered solution 3 days prior to the creation of two full-thickness wounds on the dorsum. Endostatin was administered daily until wound closure was complete. A third group received endostatin, but also had daily topical vascular endothelial growth factor applied locally to the wound. Wound area was measured daily and the wounds were analyzed for granulation tissue formation, epithelial gap, and wound vascularity. Endostatin-treated mice showed a significant delay in wound healing. Granulation tissue formation and wound vascularity were significantly decreased, but reepithelialization was not effected. Topical vascular endothelial growth factor application to wounds in endostatin-treated mice resulted in increased granulation tissue formation, increased wound vascularity, and wound closure approaching that of control mice. This study shows that the angiogenesis inhibitor endostatin delays wound healing and that topical vascular endothelial growth factor is effective in counteracting this effect.
authors.affiliation: Laboratory of Microvascular Research and Vascular Tissue Engineering, Institute of Reconstructive Plastic Surgery, New York University Medical Center, New York 10016, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Michaels
authors.forename: Michael
authors.initials: M
authors.lastname: Dobryansky
authors.forename: Robert D
authors.initials: RD
authors.lastname: Galiano
authors.forename: Kirit A
authors.initials: KA
authors.lastname: Bhatt
authors.forename: Russell
authors.initials: R
authors.lastname: Ashinoff
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Ceradini
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
mesh_terms: D000287:Administration, Topical; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D043169:Endostatins / Q000494:pharmacology; D006097:Granulation Tissue / Q000098:blood supply / Q000187:drug effects; D006133:Growth Substances / Q000008:administration & dosage*; D051379:Mice; D012867:Skin / Q000098:blood supply* / Q000187:drug effects* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D043169:Endostatins; D006133:Growth Substances; D042461:Vascular Endothelial Growth Factor A