Endothelial Dysfunction as a Target for Prevention of Cardiovascular Disease

The endothelium, once considered a mere selectively permeable barrier between the bloodstream and the outer vascular wall, is now recognized to be a crucial homeostatic organ, fundamental for the regulation of the vascular tone and structure. Indeed, endothelial cells are able to synthesize and secrete a broad spectrum of anti-atherosclerotic substances, the most characterized of which is nitric oxide (NO), a gas that is generated from the metabolism of L-arginine by endothelial NO synthase (eNOS), constitutively expressed in endothelial cells (1). Under physiologic conditions, endothelial stimulation induces the production and release of NO, which diffuses to surrounding tissue and cells and exerts its cardiovascular protective role by relaxing media-smooth muscle cells, preventing leukocyte adhesion and migration into the arterial wall, muscle cell proliferation, platelet adhesion and aggregation, and adhesion molecule expression (1,2). In disease conditions, including the presence of cardiovascular risk factors, the endothelium undergoes functional and structural alterations, thus losing its protective role and becoming a proatherosclerotic structure (1). In the earliest stages, the principal endothelial alteration is merely functional and addressed as “endothelial dysfunction. ” The fundamental feature of this condition is the impaired NO bioavailability. This can be the consequence of either a reduced production by eNOS or, more frequently, of an increased breakdown by reactive oxygen species (ROS) (1,2). In the presence of impaired NO bioavailability, the endothelium implements various physiological pathways in the attempt to compensate for NO