Activated protein C as a promoter of wound healing

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The healing of wounds is a complex process involving a number of stages, including coagulation, inflammation, remodelling and finally development of full strength skin. Impaired wound healing and-or skin ulcers occur in patients with peripheral arterial occlusive disease, deep vein thrombosis, diabetes, pressure sores and burns. Despite intense investigation, the precise mechanisms associated with impaired healing are poorly understood. APC is a serine protease that plays a central role in physiological anticoagulation. APC potently activates gelatinase A, an enzyme that plays a prominent role during the remodelling phase of wound healing and angiogenesis. Our preliminary experiments provide very strong evidence that APC accelerates wound healing using both cultured cells and a rat skin wounding model. There are three aims to this study. The first will use cell culture techniques to investigate the mechanisms of action of APC during wound healing. Secondly, we will expand our pilot studies on the effect of APC as a promoter of wound healing in vivo. These studies will examine the exact dosing and timing regime for APC, using a rat wound healing model. In addition, we will test the effect of APC on slow healing wounds, present in diabetic rats. Thirdly, we will determine whether APC is quantitatively or functionally deficient in human wound fluid derived from slow-healing wounds compared to wounds that heal normally. This is the first time that APC has been implicated in wound healing. It is envisaged that this work will ultimately lead to a novel topical treatment of APC to accelerate slow-healing wounds.