**1. Introduction**

A healthy vascular endothelium exerts atheroprotective effects through vasoactive mediators such as nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factor (EDHF). The endothelium plays an important role in regulating vasomotor tone and maintaining vascular integrity. Endothelial dysfunction, impaired

endothelium-dependent dilation, is a fundamental element in the pathogenesis of cardiovascular disease. There is evidence that as we age, the endothelium is exposed to the deleterious effects of elevated blood pressure and increased levels of cholesterol, glucose, homocysteine, to products of the inflammatory response and to components of cigarette smoke, and these protective properties decrease, leading to a state of endothelial dysfunction [1]. Although endothelial dysfunction is associated with a number of risk factors for atherosclerosis, these risk factors are not the only determinants of endothelial dysfunction. The rate of endothelial dysfunction is influenced by a number of factors that are determined by genetic variation and thus inherited in families. These issues will be addressed in this chapter.

Vascular atherosclerosis, as the most common sign of endothelial dysfunction, usually manifests itself at a later age, although studies of twins and adoptions indicate that this more common form is also partly heritable, although the inheritance is complex, arising from shared environmental exposures (risk factors) and many common gene variants (polymorphisms) with small to moderate effects. Endothelial dysfunction manifested in atherosclerosis also results from single-gene diseases that strongly modify risk factors, such as hypercholesterolemia or hyperhomocysteinuria. Children with certain single-gene disorders, such as homocystinuria and familial hypercholesterolemia, are at risk for premature atherosclerosis, and also exhibit early endothelial dysfunction [2–4].
