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. A rapidly expanding body of evidence suggests that agonists of angiogenesis may be of use in the treatment of cardiovascular diseases. This report described how PlGF offers a selective means of increasing angiogenesis in diseased tissue, in particular infarcted brain tissue. INSERM researchers have recently described a second target, Cyr61. Cyr61 is a secreted, cysteine-rich heparin-binding protein that is associated with the extracellular matrix and cell surface, and has been demonstrated to be proangiogenic in in vitro studies. These researchers have recently described the angiogenic effect of human Cyr61 in a rabbit model of hind-limb ischemia. Angiographic, hemodynamic, and histologic parameters indicated that Cyr61 gene therapy significantly improved perfusion and was in fact more impressive than VEGF(165) gene therapy. Peripheral artery occlusive disease (PAOD) otherwise known as peripheral vascular disease (PVD) or arteriosclerosis obliterans is defined as an occlusion of blood supply to the extremities by atherosclerotic plaques (atheromas), a thrombus, or an embolism. Occasionally limb ischemia condition occurs suddenly, but chronic ischemia due to gradual enlargement of an atheromatous plaque is more common. 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 Since the first-line thrombolytic has recently been withdrawn from the market, new pharmacologic options are urgently required. This data suggests that Cyr61 gene transfer may be one of a number of novel approaches to PAOD related to the increase in angiogenesis. Of course such an approach may not necessarily be restricted to PAOD and the therapeutic benefit of pro-angiogenic strategies is relevant to other major cardiovasular diseases such as stroke and myocardial infarction

December, 2002

Adapted from Fatacchioli et al, Hum Gene Ther 2002 Aug;13(12):1461-70

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