title: Endostatin inhibits ischemia-induced neovascularization and increases ischemic tissue loss.
abstract: The impact of inhibitors of tumor angiogenesis (endostatin, angiostatin) on the neovascularization required for the healing of transferred tissue has not been examined. We investigated the effect of endostatin on the functional neovascularization of random pattern flaps. C57BL6 mice were pretreated with endostatin beginning 3 days prior to surgery (n = 10), and daily injections continued throughout the study. Dorsal random cutaneous flaps were raised in both treatment and control (saline-treated) groups. The remaining cranial attachment was divided on day 9. Oxygen tension (PO2) was measured using a microprobe on days 1, 3, 5 and 16. Flaps were harvested and the vasculature was stained with CD31 on day 16. We found that endostatin significantly decreased flap survival. Mice that were treated with endostatin had fewer CD31+ blood vessels, worse flap perfusion at all time points, and lower oxygen tensions throughout the length of the flap. These findings have potential implications for the patients undergoing antiangiogenesis therapy who require surgical reconstruction.
authors.affiliation: Laboratory for Microvascular Research and Vascular Tissue Engineering, New York University School of Medicine, New York, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Dobryansky
authors.forename: Robert D
authors.initials: RD
authors.lastname: Galiano
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Cetrulo
authors.forename: Kirit A
authors.initials: KA
authors.lastname: Bhatt
authors.forename: Joseph
authors.initials: J
authors.lastname: Michaels
authors.forename: Russell
authors.initials: R
authors.lastname: Ashinoff
authors.forename: Jamie P
authors.initials: JP
authors.lastname: Levine
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D043169:Endostatins / Q000008:administration & dosage*; D007271:Injections, Intradermal; D007511:Ischemia; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012867:Skin / Q000098:blood supply; D013524:Surgical Flaps / Q000098:blood supply*
chemical_list: D020533:Angiogenesis Inhibitors; D043169:Endostatins