Nitrite/nitric oxide regulation of therapeutic angiogenesis for diabetic ischemic vascular disease

Abstract

Diabetes is associated with increased incidence of cardiovascular disease along with concomitant peripheral vascular disease contributing to development of PAD and non-healing ulcers of the extremities. Previous work has revealed that NO bioavailability is markedly diminished during diabetes and figures to be a key contributor to increased cardiovascular disease in this metabolic disorder. Our group has determined that the NO/nitrite endocrine system serves as a critical mediator of ischemic vascular remodeling of peripheral limbs and has further revealed the importance of this endocrine system for diabetic vascular disease. Data will be presented demonstrating how nitrite/NO metabolism mediates protection against peripheral tissue ischemia and necrosis during diabetes by stimulating therapeutic angiogenesis in both young and aged diabetic animal models. Nitrite/NO therapeutic angiogenesis during diabetes significantly depends on VEGF induction and activity while also significantly decreasing vascular and ischemic tissue oxidative stress. Importantly, oral sodium nitrite administration to diabetic patients with peripheral tissue ulcers is well tolerated indicating the therapeutic potential of this approach for therapeutic angiogenesis for diabetic peripheral vascular disease.