Activated protein C stimulates expression of angiogenic factors in human skin cells, angiogenesis in the chick embryo and cutaneous wound healing in rodents

Issue title: Selected Proceedings of the 6th Asian Congress for Mirocirculation (ACM'05) (Tokyo, February 25 and 26, 2005)

Article type: Research Article

Authors: Xue, Meilang | Thompson, Patrick | Sambrook, Philip N. | March, Lyn | Jackson, Christopher J.^;

Affiliations: Sutton Arthritis Research Laboratories, Institute of Bone and Joint Research, University of Sydney, NSW, Australia | Department of Rheumatology, Institute of Bone and Joint Research, University of Sydney, NSW, Australia

Note: [] Corresponding author. E-mail: cjackson@med.usyd.edu.au.

Abstract: 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.

Keywords: Activated protein C, angiogenic factors, wound healing, keratinocytes, umbilical vein endothelial cells

Journal: Clinical Hemorheology and Microcirculation, vol. 34, no. 1-2, pp. 153-161, 2006