Activated protein C stimulates expression of angiogenic factors in human skin cells, angiogenesis in the chick embryo and cutaneous wound healing in rodents.
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. We show here that APC upregulates the angiogenic promoters, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8) or matrix metalloproteinase-2 (MMP-2) in cultured human skin fibroblasts (HF), keratinocytes (HK) or umbilical vein endothelial cells (HUVE). In the chick embryo chorio-allantoic membrane assay, APC promoted angiogenesis. In a full-thickness rat skin healing model, a single topical application of APC enhanced wound healing compared to saline control. In summary, our results demonstrate that APC promotes cutaneous wound healing at least partly by stimulation of angiogenesis.
Xue
Meilang
M
Sutton Arthritis Research Laboratories, Institute of Bone and Joint Research, University of Sydney, NSW, Australia.
Thompson
Patrick
P
Sambrook
Philip N
PN
March
Lyn
L
Jackson
Christopher J
CJ
D042501:Angiogenic Proteins / Q000235:genetics*; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D002642:Chick Embryo; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D018919:Neovascularization, Physiologic; D011486:Protein C / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000166:cytology*; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects
D042501:Angiogenic Proteins; D018932:Chemokine CCL2; D016209:Interleukin-8; D011486:Protein C; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2