Abstract
Peripheral artery disease is a common disorder and a major cause of morbidity and mortality worldwide. Therapy is directed at reducing the risk of major adverse cardiovascular events and at ameliorating symptoms. Medical therapy is effective at reducing the incidence of myocardial infarction and stroke to which these patients are prone but is inadequate in relieving limb-related symptoms, such as intermittent claudication, rest pain, and ischemic ulceration. Limb-related morbidity is best addressed with surgical and endovascular interventions that restore perfusion. Current medical therapies have only modest effects on limb blood flow. Accordingly, there is an opportunity to develop medical approaches to restore limb perfusion. Vascular regeneration to enhance limb blood flow includes methods to enhance angiogenesis, arteriogenesis, and vasculogenesis using angiogenic cytokines and cell therapies. We review the molecular mechanisms of these processes; briefly discuss what we have learned from the clinical trials of angiogenic and cell therapies; and conclude with an overview of a potential new approach based upon transdifferentiation to enhance vascular regeneration in peripheral artery disease.