Endothelium and the lipid metabolism: the current understanding.

The endothelium is a dynamic organ and responds to various physical and humoral conditions. The endothelium secretes several biologically active substances, both vasoconstrictors and vasodilators, which control these processes. Endothelial function is most commonly assessed as the vasodilatory response to stimuli. Several endothelium-dependent agonists have been identified, each of which acts through a membrane receptor. Nitric oxide which is continuously synthesized by the endothelium has a wide range of biological properties that maintain vascular homeostasis. It is a potent vasodilator and inhibitor of platelet aggregation and thus has an important protective role. Endothelial dysfunction in hypercholesterolemic patients is in large part due to a reduced bioavailability of NO. Traditional coronary risk factors, especially hypercholesterolemia, produce endothelial dysfunction even in patients with normal blood vessels. The underlying mechanisms involve a local inflammatory response, release of cytokines and growth factors, activation of oxidation-sensitive mechanisms in the arterial wall, modulation of intracellular signaling pathways, increased oxidation of low-density lipoprotein cholesterol, and quenching of nitric oxide. Clinical studies have shown a significant improvement in endothelial dysfunction following lowering of serum cholesterol levels, infusion of nitric oxide donors like L-arginine and exercise training. Clinical trials are underway examining the role of endothelin-1 receptor antagonists like bosentan in the prevention of graft atherosclerosis.