Arteriogenesis in peripheral arterial disease.

Lower extremity peripheral arterial disease (PAD) most frequently presents with lower limb pain on walking--intermittent claudication. As the disease progresses the patient might suffer from rest pain and/or ischemic ulceration--critical limb ischemia (CLI). The management of patients with PAD consists of life-style modifications and pharmacotherapy addressing the risk factors to minimize the risk for disease progression and mortality in myocardial infarction and stroke. Symptomatic invasive treatment consists of surgical or endovascular revascularization. Unfortunately, about 20-30% of patients with CLI can not be treated by any of these methods and the only option for them is often amputation. For this group of patients there is a great need for alternative treatment strategies and several strategies are currently tested to stimulate collateral artery growth (arteriogenesis). Arteriogenesis is defined as growth of preexisting arteriolar connections into true collateral arteries. It relies on a complex combination of increased shear stress, different growth factors, cytokines, proteolytic enzymes and initial local inflammation. It is probable that this process is important for disease progression and the pathophysiology of leg ischemia, but its impact needs to be further elucidated. Such efforts will also benefit attempts to stimulate arteriogenesis as therapy for leg ischemia. This article briefly discusses the basic mechanisms underlying arteriogenesis, and speculates how this knowledge influences our view of the pathophysiology and treatment of PAD, particularly lower limb ischemia.