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 (for further free information please click here). Occasionally this condition occurs suddenly, but chronic occlusion 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, frequently manifesting symptoms of intermittent claudication (pain while walking that abates during rest). Other symptoms include 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). Some patients, however, are asymptomatic. In the most severe cases PAOD can cause limb-threatening ischemia and under these conditions it is important to prevent further progression of disease. PAOD is treated conservatively as a first line option, however 20-30% of patients develop more severe symptoms with worsening ischemia that requires intervention. Interventions include vascular surgery (e.g., thrombectomy 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 Since the first-line thrombolytic has recently been withdrawn from the market, new pharmacologic options are urgently required. In this respect research recently emerging from Italy is of significant importance. Proteinase-activated receptors (PAR-2) are expressed by the cardiovascular system and mediate vasodilation, plasma protein extravasation, and endothelial cell proliferation. This group has therefore investigated the ability of PAR-2 activation to improve limb ischemia. The PAR-2 activating peptide, PAR-2AP increased capillarity in normoperfused adductor skeletal muscles. Perhaps more importantly, PAR-2AP and the PAR-2 agonist trypsin enhanced the reparative angiogenic response to limb ischemia. Potentiation of reparative angiogenesis by PAR-2AP or trypsin resulted in an accelerated hemodynamic recovery and enhanced limb salvage. This study is the first to demonstrate the angiogenic potential of PAR-2 stimulation in vivo and supports the therapeutic development of PAR-2 activators.

Entry date October, 2002

Adapted from Milia et al, Circ Res 2002 Aug 23;91(4):346-52

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