The endothelium is an essential structural and functional element of the cardiovascular system and constitutes the largest endocrine system in the organism. It contributes to cardiovascular homeostasis not only by regulating vascular permeability but also by adjusting the calibre of blood vessels to haemodynamic and hormonal demands and by maintaining blood fluidity. Endothelial cells perform these functions by the expression, activation, and release of powerful vasoactive substances as well as of numerous other bioactive molecules. Almost all conventional risk factors for atherosclerosis are associated with endothelial dysfunction. Cardiovascular risk factors activate a number of pro-oxidative genes in the vascular wall resulting in the generation of reactive oxygen species that ultimately promote endothelial release of transcriptional and growth factors, proinflammatory cytokines, chemoattractant substances and adhesion molecules.¹ This complex cascade of events underlies the transition from normal endothelial function to endothelial dysfunction that manifests itself by abnormal vasomotor activity, development of a procoagulant endothelial surface, inflammation and, finally, plaque formation.

One of the earliest manifestations of increased vascular oxidant stress and endothelial dysfunction is a decreased production and/or local bioavailability of nitric oxide. Clinical measurements of endothelium-dependent vasodilation by a variety of different methodologies provide a marker of endothelial integrity and are an “excellent barometer” of vascular health that can be used to gauge cardiovascular risk.² In fact, several studies indicate that endothelial dysfunction, assessed as impaired endothelium-dependent flow-mediated vasodilation (FMD), predicts an increased rate of adverse cardiovascular events, including acute coronary syndromes, ischaemic stroke, critical limb …