Activated protein C prevents inflammation yet stimulates angiogenesis to promote cutaneous wound healing

Activated protein C (APC) is a serine protease that plays a central role in physiological anticoagulation, and has more recently been shown to be a potent anti‐inflammatory mediator. Using cultured human cells, we show here that APC up‐regulates the angiogenic promoters matrix metalloproteinase‐2 in...

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Published in:Wound repair and regeneration 2005-05, Vol.13 (3), p.284-294
Main Authors: Jackson, Christopher J., Xue, Meilang, Thompson, Patrick, Davey, Ross A., Whitmont, Kaley, Smith, Susan, Buisson-Legendre, Nathalie, Sztynda, Tamara, Furphy, Louise J., Cooper, Alan, Sambrook, Philip, March, Lyn
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Cell Proliferation - drug effects
Cells, Cultured
Chick Embryo
Humans
Inflammation - immunology
Matrix Metalloproteinase 2 - biosynthesis
Matrix Metalloproteinase 2 - drug effects
Neovascularization, Physiologic - drug effects
Protein C - pharmacology
Rats
Skin - drug effects
Skin - immunology
Wound Healing - drug effects
Wound Healing - immunology
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Summary:Activated protein C (APC) is a serine protease that plays a central role in physiological anticoagulation, and has more recently been shown to be a potent anti‐inflammatory mediator. Using cultured human cells, we show here that APC up‐regulates the angiogenic promoters matrix metalloproteinase‐2 in skin fibroblasts and umbilical vein endothelial cells, vascular endothelial growth factor in keratinocytes and fibroblasts, and monocyte chemoattractant protein‐1 in fibroblasts. In the chick embryo chorioallantoic membrane assay, APC promoted the granulation/remodeling phases of wound healing by markedly stimulating angiogenesis as well as promoting reepithelialization. In a full‐thickness rat skin‐healing model, a single topical application of APC enhanced wound healing compared to saline control. APC‐treated wounds had markedly more blood vessels on day 7 and a significantly lower infiltration of neutrophils at days 4 and 7. The broad spectrum matrix metallo‐proteinas, GM6001, prevented the ability of APC to promote wound healing. In summary, our results show that APC promotes cutaneous wound healing via a complex mechanism involving stimulation of angiogenesis and inhibition of inflammation. These unique properties of APC make it an attractive therapeutic agent to promote the healing of chronic wounds.
ISSN:1067-1927
1524-475X
DOI:10.1111/j.1067-1927.2005.00130311.x