Current strategies and perspectives for correcting endothelial dysfunction in atherosclerosis

The vascular endothelium synthesizes and releases a spectrum of vasoactive substances such as nitric oxide and endothelin. In atherosclerosis, the delicate balance between endothelium-derived factors is disturbed. Endothelin acts as the natural counterpart to endothelium-derived nitric oxide, which exerts vasodilating, antithrombotic and antiproliferative effects, and inhibits leukocyte adhesion to the vascular wall. Besides its blood pressure increasing effect in man, endothelin also induces vascular and myocardial hypertrophy, which are independent risk factors for cardiovascular morbidity and mortality. The derangement of endothelial function in atherosclerosis is likely to be caused in part by genetic factors, but is also due to cardiovascular risk factors. Endothelial dysfunction in atherosclerosis is crucial for the development of the disease process in the vasculature and is therefore an important therapeutic target. However, the efficacy of pharmacotherapy aimed at an improvement in endothelial function depends on the individual risk factor profile of the patient.