The role of NOS3 in stem cell mobilization

In response to injury, stem cells are mobilized from the bone marrow into the circulation and home to sites of ischemia, where they contribute to the formation of new blood vessels. This mobilization is mediated by proteinases. Matrix metalloproteinase-9 (MMP-9) is essential for the mobilization that is induced by growth factors (such as vascular endothelial growth factor, VEGF) and cytokines (such as stromal-cell-derived factor-1). The mechanism by which MMP-9 and VEGF interact to promote stem cell mobilization is gradually being unraveled. Here, the activation of NOS3 (endothelial nitric oxide synthase) in the bone marrow microenvironment is emphasized as one such mechanistic link and a potential therapeutic target for patients with chronic cardiovascular disease.