Peripheral artery disease: therapeutic advances

Abstract

Peripheral arterial disease (PAD), usually caused by atherosclerosis, is defined as an obstructive arterial disease of the lower extremities that reduces arterial flow during exercise or, in advanced stages, at rest. It affects more than 8.5 million people in the USA. PAD may appear as an asymptomatic arterial disease with abnormal noninvasive test results, or as a symptomatic disease presenting with atypical limb pain, classic intermittent claudication, or critical limb ischemia. The spectrum of PAD is not a continuum. Patients who present with critical limb ischemia may have experienced minimum symptoms. PAD results in limitation of exercise and walking ability, described as intermittent claudication. Patients with PAD are physically impaired and have a higher risk of cardiovascular events; therefore, the treatment goals are aimed at decreasing their cardiovascular risk, as well as improving exercise and daily functional performance. Apart from supervised exercise, which is a major treatment modality for patients with PAD, as of yet there have been very few significant pharmacological breakthroughs in the treatment of PAD that increases blood flow to the ischemic limb. Although percutaneous intervention has markedly improved the treatment of PAD, bypass surgery continues to play an important role. For the most part medical therapy for PAD is designed as a secondary prevention for cardiovascular risk. These include antiplatelet therapy, statins, ACE-inhibitors, smoking cessation and possibly antihypertensive therapy. Revascularization is most beneficial for patients with lifestyle limiting symptoms, acute or chronic limb ischemia with resting pain or nonhealing ulcers. In the following review article we will try to explore the clinical role of some of the latest developments in this field.

A stromal cell-derived factor-1 releasing matrix enhances the progenitor cell response and blood vessel growth in ischaemic skeletal muscle

“…In particular, PAD affl icts an estimated 27 million people in Europe and North America (Belch et al, 2003). This disease manifests when the fl ow of blood to extremities is acutely or chronically reduced (Selvin and Erlinger, 2004;Shamoun et al, 2008). Attributed to the lack of blood fl ow, symptoms typically include: pain, cramping, weakness and a poor ability to heal.…”

Arteriogenic Revascularization Does Not Induce Vascular Function Impairment

“…This reduction of blood flow to peripheral tissues is due to occlusion and narrowing of the vascular luminal space [15]. In most cases this obstruction is due to atherosclerosis (Figure 3), where extracellular cholesterol will build up along damaged/torn sections of arterial walls and be covered in a thin layer of fibrotic tissue [16].…”

“…This stenosis reduces volumetric blood flow via Poisseuille's Law. The resultant blood flow insufficiency (ischemia) is a detriment to the health of the extremities and must be ameliorated by vascular growth or by breaking apart or minimizing occlusions [15]. Further, while the resting blood supply is affected by this condition, vascular function (blood flow control) is also impaired (as previously mentioned).…”

“…However, the causes for the ischemic conditions in the models are significantly different than those inducing ischemia in PAD. Ischemia with PAD is a result of atherosclerosis, which occurs chronically, via gradual build-up of plaque and narrowing of the arteries over many years [15]. Complete occlusion of arteries often results in limb necrosis without proper treatment (10-40% have primary amputations and there is a mortality rate of 40-70% in 5 years) [54].…”

“…The gradual arterial narrowing of atherosclerosis also results in a slower impairment of blood flow and progression of hypoxia, which may result in a different timeline for vascular repair. Additionally, atherosclerosis is often found at multiple vascular sites in the circulatory system of the extremities [15]. However, the surgical mouse models result in arterial occlusion at one point in the femoral artery.…”