Endothelial dysfunction: a key to the pathophysiology and natural history of peripheral arterial disease?

Dysfunctional endothelium plays a crucial role in all stages of atherosclerosis and thus the accurate assessment of this organ is a valuable tool, especially if such assessments are clinically relevant. In peripheral arterial disease (PAD), which affects about 27 million of individuals in Europe and North America, increased plasma markers of endothelial dysfunction and reduced endothelium-mediated vasoreactivity, are associated with both the severity and the extent of atherosclerosis in the arteries of the lower limbs, is exacerbated by acute exercise, may help identify subjects with subclinical coronary artery disease, and portends a worse outcome. As a result, endothelial dysfunction is a promising target for therapeutic interventions in PAD. Large clinical trials are needed to verify whether affected individuals with depressed endothelial function benefit from specific treatments.