The healthy vascular endothelium exerts atheroprotective actions through vasoactive mediators such as nitric oxide (NO), prostacyclin, and endothelium derived hyperpolarising factor (EDHF). There is evidence that as the endothelium ages, it is exposed to the damaging effects of raised blood pressure and increased concentrations of cholesterol, glucose, homocysteine, to products of the inflammatory response, and to the constituents of cigarette smoke, and these protective properties diminish leading to a state of endothelial dysfunction.¹ Endothelial dysfunction can be detected in forearm or coronary arteries in vivo, before the development of clinical atherosclerosis, as an impairment of endothelium dependent agonist or flow mediated vasodilation.² Endothelial dysfunction by these methods correlates with cardiovascular risk factors,³ and may be predictive of incident cardiovascular events.⁴

Children with certain single gene disorders such as homocystinuria and familial hypercholesterolaemia, at risk of premature atherosclerosis, also exhibit early endothelial dysfunction.^5,6 Although the more common forms of atherosclerosis manifest later in life, twin and adoption studies indicate that this more common form is also partly heritable,⁷ though inheritance is complex, arising as a result of common environmental exposures (risk factors) and many common gene variants (polymorphisms) with small to moderate effect. In common with other complex disorders, the causative genes have been difficult to identify. There have been few studies evaluating the heritability of endothelial function. However, vessels in the offspring or relatives of patients with premature cardiovascular disease show structural and functional changes more commonly, even before clinically manifest disease.^8,9 Therefore, individual differences in endothelial function, and hence susceptibility to later atherosclerosis, might relate not only to different levels of exposure to risk factors but also to inter-individual differences in the carriage of risk alleles of genes expressed in the vascular endothelium. The atheroprotective actions of endothelial mediators such …