Nitric oxide and the angiogenic response: can we improve the results of therapeutic angiogenesis?

Therapeutic angiogenesis has yielded promising results in animal models, including the demonstration of newly created blood vessels, increased perfusion and functional benefits. On the other hand, clinical studies using similar methods of angiogenesis have so far been disappointing. The possibility that endothelial dysfunction may play a role in this bench-to-bedside discrepancy has led to further research on the role of endothelial-derived mediators in the angiogenic cascade. One of these mediators is nitric oxide (NO), which plays an integral role in the development and maintenance of a microvascular network and whose local availability is altered in endothelial dysfunction. This article outlines the role of NO in the angiogenic response and discusses possible therapeutic options to optimise endothelial dysfunction and NO availability in patients undergoing angiogenic therapy.