Time course analysis of hypoxia, granulation tissue and blood vessel growth, and remodeling in healing rat cutaneous incisional primary intention wounds

Lokmic, Z, Darby, I, Thompson, E and Mitchell, G 2006, 'Time course analysis of hypoxia, granulation tissue and blood vessel growth, and remodeling in healing rat cutaneous incisional primary intention wounds', Wound Repair And Regeneration, vol. 14, pp. 277-288.


Document type: Journal Article
Collection: Journal Articles

Title Time course analysis of hypoxia, granulation tissue and blood vessel growth, and remodeling in healing rat cutaneous incisional primary intention wounds
Author(s) Lokmic, Z
Darby, I
Thompson, E
Mitchell, G
Year 2006
Journal name Wound Repair And Regeneration
Volume number 14
Start page 277
End page 288
Total pages 12
Publisher Blackwell Publishing
Abstract Hypoxia and the development and remodeling of blood vessels and connective tissue in granulation tissue that forms in a wound gap following full-thickness skin incision in the rat were examined as a function of time. A 1.5 cm-long incisional wound was created in rat groin skin and the opposed edges sutured together. Wounds were harvested between 3 days and 16 weeks and hypoxia, percent vascular volume, cell proliferation and apoptosis, alpha-smooth muscle actin, vascular endothelial growth factor-A, vascular endothelial growth factor receptor-2, and transforming growth factor-beta(1) expression in granulation tissue were then assessed. Hypoxia was evident between 3 and 7 days while maximal cell proliferation at 3 days (123.6 +/- 22.2 cells/mm(2), p < 0.001 when compared with normal skin) preceded the peak percent vascular volume that occurred at 7 days (15.83 +/- 1.10%, p < 0.001 when compared with normal skin). The peak in cell apoptosis occurred at 3 weeks (12.1 +/- 1.3 cells/mm(2), p < 0.001 when compared with normal skin). Intense alpha-smooth muscle actin labeling in myofibroblasts was evident at 7 and 10 days. Vascular endothelial growth factor receptor-2 and vascular endothelial growth factor-A were detectable until 2 and 3 weeks, respectively, while transforming growth factor-beta(1) protein was detectable in endothelial cells and myofibroblasts until 3-4 weeks and in the extracellular matrix for 16 weeks. Incisional wound granulation tissue largely developed within 3-7 days in the presence of hypoxia. Remodeling, marked by a decline in the percent vascular volume and increased cellular apoptosis, occurred largely in the absence of detectable hypoxia. The expression of vascular endothelial growth factor-A, vascular endothelial growth factor receptor-2, and transforming growth factor-beta(1) is evident prior, during, and after the peak of vascular volume reflecting multiple roles for these factors during wound healing.
Subject Cell Physiology
Keyword(s) Cell Biology
Dermatology
Medicine
Research & Experimental
Surgery
DOI - identifier 10.1111/j.1743-6109.2006.00122.x
Copyright notice © 2006 by the Wound Healing Society
ISSN 1067-1927
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