The Anti-angiogenic VEGF165b and VEGFR1 Signaling in Peripheral Artery Disease

Project Narrative – Public Health Relevance Peripheral arterial disease (PAD) is a major health problem that afflicts millions of patient in the United States. PAD is caused by atherosclerosis that impairs blood flow to the legs. PAD is crippling disease and there are no medical therapies that have the ability to improve blood flow to the legs of patients suffering from PAD. Angiogenesis is defined as the growth and proliferation of blood vessels from existing vascular structures. Attempting to grow blood vessels to treat patients with PAD has been a focus of human therapy for decades but trials clinical trying to grow blood vessels have consistently failed. Vascular endothelial growth factor (VEGF) is perhaps the best studied agent that has been tried in humans. We and others have recently reported on a poorly described variant of VEGF. Our work suggest that this inhibitory form of VEGF works in a way that is very different than has been proposed and may explain why a role for one the VEGF receptors (VEGF being the key and the receptor being the lock) has been poorly understood. Perhaps of equal importance our work may provide an explanation for the high rate of heart attack and strokes that afflicts this population. We will build on these finding in three specific aims and believe these results will rapidly allow for the development of new treatments for patients with PAD.