468. Tissue Factor as a Link between Wounding and Tissue Repair

Abstract

Top of pageAbstract Delayed healing of cutaneous wounds in diabetes is associated with reduced vascular endothelial growth factor (VEGF) expression and impaired recruitment of smooth muscle cells. Consistent with the concept that low levels of tissue factor (TF) might be associated with diminished VEGF expression, we explore skin wound healing, in which decreased cell proliferation and angiogenesis might be explained by a relative impairment in local TF induction. NOD mice were used in the experiments. Skin wounds were generated at both sides of the lower dorsal trunk. Local somatic gene transfer of TF was achieved by liposomal mediated transfection. Wound and wound samples were evaluated at designated time point for size, gene expression pattern and blood vessel and flow. In diabetes, TF induction in response to cutaneous wounding which ordinarily precedes increased expression of VEGF and a-smooth muscle actin (SMA) transcription, is diminished. Enhanced TF expression in wounds of diabetic mice increased VEGF transcription and translation, and enhanced formation of new blood vessels and elevated blood flow. Increased levels of TF in wounds of diabetic mice enhanced wound healing. The time to achieve 50% wound closure was reduced from 5.5 days in untreated diabetic mice to 4.1 days in animals undergoing TF gene transfer. Cutaneous wounds in diabetic mice display a relative deficiency of TF, thereafter, contributes to delayed wound repair. These data establish TF expression as an important link between the early inflammatory response to cutaneous wounding and reparative processes.