108 HIF‐I and VEGF Regulation in Ischemia

Abstract

Epithelialization and vascularization are key elements involved in the repair of cutaneous wounds. One method of regulation for these pathways is expression of a signaling molecule known as Vascular Endothelial Growth Factor (VEGF), which, in turn, is regulated by the transcription factor Hypoxia‐Inducible Factor‐1 (HIF‐1). It has been suggested that chronic wounds, which are most commonly located in ischemic tissue among the elderly, may be the result of a loss of function in the VEGF regulation pathway. Using our rat back flap model, which demonstrates the negative influences of age and ischemia on wound healing, we examined the relative expression of HIF‐1 and VEGF in aged and young rats at 3,7, and 10 days post‐wounding. Four full‐thickness biopsy punches (7 mm) were made on the back of each aged and young rat. The rostral wound pair was made ischemic by raising a transverse flap (1.8 cm wide × 8 cm length). The caudal wound pair served as a non‐ischemic control. Inserting a sterilized polyethylene sheet under both ischemic and nonischemic wounds prevented wound contraction. RNA was extracted from the tissue at the specified time points, and run on Real‐Time PCR to determine relative expression of VEGF and HIF‐1. Preliminary data suggest that, at the 3 day time point, there is a significant increase in both HIF‐1 and VEGF expression in young rats under ischemic conditions and a significant increase in VEGF expression in aged rats under ischemia with a strong (but not significant) trend towards increase in HIF‐1 as well. While the rat model does not produce significant differences between aged and young animals, this upregulation under ischemia indicates that HIF‐1 and VEGF expression may play a vital role in the early signaling of ischemic wound repair.