Stromal Cell–Derived Factor-1–Mediated Angiogenesis for Peripheral Arterial Disease

Abstract

Atherosclerotic peripheral arterial disease (PAD) is a major cause of morbidity in Western societies and significantly reduces quality of life in affected individuals.1 The prevalence of PAD is dependent on the age of the population studied, the atherosclerotic risk factor profile, and the criteria used for diagnosis. In the United States, an estimated 20% of adults >70 years of age have PAD. Only one fifth of patients with objective evidence of PAD have the typical symptoms of intermittent limb claudication, whereas a significant percentage (30% to 50%) report atypical leg symptoms, and the remainder are asymptomatic.2,3 Although relatively few deaths are directly attributed to PAD, the disease is potently implicated in mortality. Both symptomatic PAD and asymptomatic PAD independently predict cardiovascular mortality. Moreover, occlusive PAD can progress to critical limb ischemia, a condition characterized by resting perfusion that is inadequate to maintain tissue viability. Patients with chronic critical limb ischemia have a 1-year mortality of 25% and a substantial rate of limb loss.4 Although the goal of treatment in patients with limb-threatening ischemia is to preserve life and limb and to maintain function through the use of surgical or endovascular revascularization strategies, a significant number of patients have unreconstructable disease. Approximately 40% of these patients will require a major amputation within 6 months of the initial diagnosis.2 Successful treatment of these patients requires new therapeutic approaches to reconstitute the microvasculature. Article see p 1306 Over the last 20 years, the explosion in our understanding of the regulation of angiogenesis resulted in identification of mediators capable of promoting new vessel formation in ischemic tissues. …