Angiopoietin-1, angiopoietin-2 and Tie-2 receptor expression in human dermal wound repair and scarring.
BACKGROUND
The angiopoietin (Ang)/Tie-2 ligand/receptor system is known to interact with the vascular endothelial growth factor (VEGF) pathway to determine the fate of blood vessels during angiogenesis. However, the precise contribution of this system to angiogenesis and the mechanisms of vascular maturation and remodelling in human tissue repair have yet to be elucidated.


OBJECTIVE
To examine the spatial and temporal expression of Ang-1, Ang-2, Tie-2 and VEGF in relation to angiogenesis in human surgical wounds.


METHODS
Punch biopsies were taken either from normal unwounded skin (controls) during surgery or from mastectomy scars between 3 days and 2 years postsurgery. Ang-1, Ang-2, Tie-2 and VEGF fibroblast/myofibroblast and endothelial expression were characterized by immunohistochemistry, analysed semiquantitatively and correlated with microvessel density (MVD) and scar age.


RESULTS
The expression of VEGF, Ang-1, Ang-2 and Tie-2 in fibroblasts/myofibroblasts was increased significantly in early scars, decreased in older scars and was related to scar age (P < 0·001) and MVD (P < 0·0004), with strong correlations between all factors. In contrast, vascular expression of Ang-1 was decreased slightly in early scars, vascular Ang-2 remained constant and Tie-2 vascular expression increased, although there were no correlations with scar age or MVD.


CONCLUSIONS
These data demonstrate that angiopoietins and their receptor, Tie-2, are expressed in both fibroblasts/myofibroblasts and endothelial cells in healing human wounds. Fibroblast/myofibroblast expression correlates with angiogenesis and VEGF expression, suggesting a role for the angiopoietin/Tie-2 system in normal wound repair and scarring.
Staton
C A
CA
Microcirculation Research Group, Academic Unit of Surgical Oncology, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield S10 2RX, UK. c.a.staton@shef.ac.uk
Valluru
M
M
Hoh
L
L
Reed
M W R
MW
Brown
N J
NJ
D042683:Angiopoietin-1 / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000378:metabolism*; D001706:Biopsy; D002921:Cicatrix / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D058628:Myofibroblasts / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D042787:Receptor, TIE-2 / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2