Cartilage oligometric matrix protein-angiopoietin-1 promotes revascularization through increased survivin expression in dermal endothelial cells of skin grafts in mice

Am J Pathol. 2007 Nov;171(5):1682-90. doi: 10.2353/ajpath.2007.070142. Epub 2007 Sep 20.

Abstract

The present study examined the effects of cartilage oligometric matrix protein angiopoietin-1 (COMP-Ang1) on the revascularization of mice skin grafts. Full-thickness skin grafts were autotransferred into BALB/c mice. The donor grafts were soaked in COMP-Ang1 protein (50 mug/ml, n = 10) or in bovine serum albumin (BSA) (50 mug/ml, n = 10) dissolved in 1 ml of sterile, phosphate-buffered saline for 5 minutes before transfer. Revascularization of the grafts was monitored using an intravital microscope on postoperative days 3, 4, and 5. Morphological and immunohistochemical analyses were performed to evaluate platelet-endothelial cell adhesion molecule-1 and survivin expression and apoptotic signal in the transplanted grafts. Grafts soaked in COMP-Ang1 (COMP-Ang1 group) showed significantly increased revascularization compared with grafts soaked in BSA (BSA group) on intravital microscopy and platelet-endothelial cell adhesion molecule-1 staining. The COMP-Ang1 group showed a significant increase of survivin expression in the endothelial cells and a reduction of apoptotic signal in comparison to the BSA group. Therefore, we believe that COMP-Ang1 provides the therapeutic benefit of enhancing the survival of vascular endothelial cells during transplantation of skin graft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Dermis / blood supply*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Inhibitor of Apoptosis Proteins
  • Mice
  • Mice, Inbred BALB C
  • Microtubule-Associated Proteins / biosynthesis*
  • Neovascularization, Physiologic / drug effects*
  • Oxidative Stress
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Recombinant Fusion Proteins / pharmacology*
  • Repressor Proteins
  • Skin Transplantation*
  • Survivin

Substances

  • Birc5 protein, mouse
  • COMP-Ang1 fusion protein
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Survivin