Impaired wound healing in septic patients results in the need for re-operation and/or prolonged medical care in many instances. The process of tissue repair involves the formation of new blood vessels to provide the nutrients and growth factors necessary for the repair. Preliminary work from our laboratory provides evidence for impaired angiogenesis in cutaneous wound during the hyperdynamic, hypermetabolic septic state. The overall goal of this investigation is to evaluate the molecular mechanisms responsible for the inhibition of angiogenesis in healing wounds during systemic infection. Our hypothesis is that defects in the synthesis of pro-angiogenic peptides and their receptors are responsible for impaired blood vessel formation in cutaneous wounds during systemic infection. In order to test this hypothesis we will investigate the effects of systemic infection on the expression of the pro-angiogenic peptides: vascular endothelial growth factor (VEGF), and angiopoietin, with their respective receptors. We will utilize a microendothelial cell culture system to measure the capacity of wound fluid from septic and control animals to stimulate or inhibit new blood vessel fomation in vitro. This approach should allow us to isolate the specific factors responsible for impaired angiogenesis in healing wounds during the septic insult.
