NOS3 and peripheral arterial disease: CRP (C-reactive protein) has multiple roles in both the evolution of PAD and the abnormal glucose regulation [27]: it increases the production of procoagulant tissue factor, chemotactic substances, and leukocyte adhesion molecules; it affects the vascularization by prohibiting the endothelial nitric oxide synthase which normally produces nitric oxide (NO) by switching to a different pathway which is phosphoinositol-3-kinase dependent [8,10]; it alters the fibrinolysis by blocking the formation of PAI-1 (plasminogen activator inhibitor).