Angiogenesis represents an emerging therapeutic target which by 2006, is expected to command a market of $1.75 billion. Both stimulators and inhibitors of angiogenesis are being developed. Inhibitors are being developed for the treatment of cancer and more recently for the treatment of rheumatoid arthritis. On the other hand, stimulators of angiogenesis are being developed for the treatment of ischemic diseases. In the Focus on Angiogenesis section of this edition of TherapeuticAdvances we highlight how stem cell treatment can improve angiogenesis and cardiac function following myocardial infarction. Likewise in a previous dossier we describe how angiogenic growth factors such as platelet-derived growth factor (PlGF) can be used in the angiogenic treatment of cardiovascular diseases including ischemic stroke. Like myocardial infarction and stroke, peripheral artery occlusive disease (PAOD) otherwise known as peripheral vascular disease (PVD) or arteriosclerosis obliterans is an ischemic disorder caused by vascular occlusion by atherosclerotic plaques (atheromas), a thrombus, or an embolism. PAOD is a common condition with variable morbidity affecting mostly men and women older than 50 years. Based on incidence rates extrapolated to today's increasingly aging population, PAOD affects as many as 10 million people in the United States including 5% of people aged 50 or over. As the population ages, the family physician will be faced with increasing numbers of patients complaining of symptoms of lower extremity PAOD. Nearly 25% of patients remain undiagnosed until a major limb-threatening occlusion occurs. The condition can be seriously debilitating, and in the most severe cases PAOD can cause limb-threatening ischemia. Interventions include vascular surgery or bypass surgery and thrombolysis by catheter-directed intra-arterial thrombolytics. Since the first-line thrombolytic has recently been withdrawn from the market, new pharmacologic options are urgently required.

Studies have shown that fibroblast growth factor (FGF)-1, FGF-2, and FGF-5, like PlGF and vascular endothelial growth factor (VEGF), induce therapeutic angiogenesis. More recently a group of Finnish researchers have investigated the potential of FGF-4 to stimulate therapeutic neovascularization. Adenoviral gene transfer of FGF-4 to rabbits with experimental hind limb ischemia resulted in increases in vascular permeability and edema in transduced muscles 6 days after the gene transfer. Likewise, collateral growth, popliteal blood flow, and muscle perfusion was also increased. A similar effect was observed with VEGF. This study demonstrates for the first time that FGF-4 induces vascular permeability, therapeutic angiogenesis, and arteriogenesis comparable to that of VEGF and could be useful for the treatment of peripheral vascular disease.

Entry date January, 2003

Adapted from Rissanen et al, FASEB J 2003 Jan;17(1):100-2 - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.