ABSTRACT
Since the demonstration of the obligatory role of the endothelium in arterial relaxation
by Furchgott and Zawadzki (1980), there has been great interest in the role of the
endothelium in vascular disease. Apart from endothelium-dependent vasodilation, other
important functions of the endothelium have now been studied, that is, the regulation
of adhesion and infiltration of leukocytes and inhibition of platelet adhesion and
aggregation. Many functions of the endothelium are influenced by nitric oxide (NO),
which is synthesized by endothelial NO synthase. Endothelial dysfunction in hypercholesterolemic
patients is in large part due to a reduced bioavailability of NO. Multiple factors
contribute to this, including increased inactivation of NO by radicals and inhibition
of NO formation by different mechanisms. The functional implications of endothelial
dysfunction are not completely defined. However, recent studies suggest that endothelial
dysfunction contributes to myocardial perfusion abnormalities. Furthermore, endothelial
dysfunction may play an important role with respect to development and progression
of atherosclerosis because the endothelium is involved in the regulation of key events
of the atherosclerotic process. Endothelial dysfunction in hypercholesterolemia is
reversible by cholesterol-lowering treatment, that is treatment with HMG-CoA-reductase
inhibitors. First experimental data suggest that maneuvers that increase the bioavailability
of NO in hypercholesterolemia may even result in regression of preexisting atherosclerotic
lesions.
KEYWORD
Endothelium - nitric oxide - hypercholesterolemia - oxidative stress - atherosclerosis
