Novel therapeutic targets for preserving a healthy endothelium: strategies for reducing the risk of vascular and cardiovascular disease.

The endothelium lies in a strategic anatomical position between the circulating blood and the vascular smooth-muscle cells. It is a source of vasodilators such as nitric oxide, prostacyclin, and hyperpolarizing factor as well as heparin-like substances and other molecules with antiproliferative properties. These effects of endothelial cells may explain why platelets and monocytes usually do not adhere at the blood vessel wall. However, under pathological conditions, endothelial dysfunction occurs and significantly contributes to the increase of platelet- -vessel wall interaction, vasoconstriction, pro-inflammation, and proliferation. Under these conditions, endothelium-dependent vasodilation is reduced, and endothelium-dependent constrictor responses are augmented. Upon vessel wall injury, the platelets rapidly adhere to the exposed sub-endothelial matrix, which is mediated by several cellular receptors present on platelets or endothelial cells and various adhesive proteins. Subsequent platelet activation results in the recruitment of additional platelets and the generation of platelet aggregates, so forming a stable platelet plug. Therapeutic strategies aimed at improving or preserving endothelial function therefore may be promising in terms of preventing and treating coronary artery disease. Diagnostic modalities for assessing endothelial function should allow for the early detection of vascular endothelial dysfunction before the manifestation of serious adverse vascular disorders.