Endothelial dysfunction in the pathogenesis of atherosclerosis

Abstract

A healthy endothelium plays a central role in cardiovascular control. Therefore, endothelial dysfunction (ED), which is characterized by an imbalance between relaxing and contracting factors, procoagulant and anticoagulant substances, and between pro-inflammatory and anti-inflammatory mediators, may play a particularly significant role in the pathogenesis of atherosclerosis. ED is closely related to different risk factors of atherosclerosis, to their intensity and their duration. The involvement of risk factors in ED is also supported by results of intervention studies that showed regression of ED with treatment of risk factors. The common denominator whereby different risk factors cause ED is most probably increased oxidative stress and/or inflammation. ED promotes atherosclerosis and probably plays an important role in the development of thrombotic complications in the late stages of the disease. As ED is a key underlying factor in the atherosclerotic process, markers of endothelial abnormalities have been sought. Detection of ED is based on tests of endothelium-dependent vasomotion (dilation capability of peripheral and coronary arteries) and on circulating markers of endothelial function (endothelin-1, von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor, adhesion molecules). Using these tests it is possible to follow the dose-response of harmful effects or risk factors, and the effects of preventive procedures on vessel wall function.