Abstract 11798: The Nitric Oxide-Donor MPC-1011 Stimulates Angiogenesis and Arteriogenesis and Improves Hindlimb Ischemia via a cGMP-dependent Pathway Involving VEGF and SDF-1 Alpha

Introduction: Peripheral arterial disease (PAD) is an important cause of morbidity and mortality with little effective treatment currently available. Occlusive atherosclerosis in lower limbs occurs as a last step of endothelial nitric oxide (NO) deficiency limiting signal transduction necessary for normal vascular function. Thus, delivery of NO appears to be an attractive therapeutic option in several cardiovascular conditions. Hypothesis: We hypothesized that the NO-donor MPC-1011 might elicit vasodilation, angiogenesis and arteriogenesis and in turn improve limb perfusion, in a hindlimb ischemia model. Methods: Hindlimb ischemia was induced by femoral artery ligation in rats which were randomized to receive placebo, MPC-1011, cilostazol or both, for up to 28 days. Blood flow was assessed by laser Doppler imaging, angiogenesis and arteriogenesis by immunohistochemistry post mortem, and tissue VEGF, SDF-1 and cGMP levels by ELISA. Results: After femoral artery occlusion, limb perfusion in rats receiving e...