Although thrombosis is most commonly associated with myocardial infarction and stroke, other serious medical conditions including peripheral arterial occlusive disease (PAOD) also result from pathological clotting. PAOD affects mostly men and women older than 50 years, those particularly at risk are individuals with heart disease and/or diabetics. PAOD is thought to affects as many as 10 million people in the United States and is caused by the chronic occlusion of peripheral arteries, normally those in the leg and is associated with variable morbidity. Nearly 25% of patients remain undiagnosed until there is a life-threatening ischemia of a limb. The condition can be seriously debilitating, frequently manifesting symptoms of intermittent claudication (pain while walking that abates during rest), numbness or weakness in the legs, aching pain in the feet or toes while at rest, non-healing ulcers on the leg or foot, cold legs or feet, and skin color changes of the legs or feet (particularly dependent rubor). Pharmacological treatment options for PAOD include the use of thrombolytics or molecules able to stimulate angiogenesis. One such molecule, PlGF is described in the "Licensing Opportunities" section of this edition of TherapeuticAdvances, however a variety of other growth factors have also been implicated in the process of angiogenesis. Once endothelial cells have escaped their basement membrane, they enter the extracellular matrix moving towards target tissue undergoing proliferation as they migrate. This process is under the influence of a number of growth factors including VEGF and bFGF (basic Fibroblast Growth Factor). During angiogenesis, low-molecular weight FGF-2 increases endothelial motility, proliferation and proteinase activity, and modulates integrin levels. High-molecular weight FGF-2 may act on endothelial cell proliferation after nuclear translocation in the endothelial cells. Thus rFGF-2 has been shown to improve perfusion in models of myocardial and hindlimb ischemia. Recent reports take this body of research one step forward showing that in patients with intermittent claudication caused by atherosclerosis, intra-arterial rFGF-2 was able to significantly increase peak walking by 34%. This report thus establishes a clinical proof of concept for the therapeutic use of angiogenesis stimulating molecules in the treatment of PAOD and its manifestations including intermittent claudication.

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