Weninger and colleagues, 1 in this issue of Circula-tion Research, have simply and elegantly reported on a piece of fundamental arterial biology totally unexplored before: the developmental origins of the intima in the siphon of the internal carotid artery. This site was chosen for study because the parasellar internal carotid artery in adults has the unwelcome fate of being highly prone to atherosclerosis at a site where the outcome is stroke. Moreover, this site, like the origin of the left anterior descending coronary artery, develops a focal intimal thickening long before the usual changes of lipid accumulation, characterized as “atherosclerosis,” occur. It is very reasonable, therefore, to consider the developmental biology of such sites as very early events that set the scene for localization of atherosclerosis in adults. Particularly intriguing is their evidence that the shape of the vessel, rather than the flow patterns, may determine the degree of intimal hyperplasia and ultimately constitute a risk factor for development of clinically important lesions at this critical site.

The surprise is that this is only the second atherosclerosisprone site to be studied at such an early stage. There are very few studies of developmental intimal formation at any site, despite our knowledge that this tissue, the arterial intima, is the normal tissue, the “soil,” in which atherosclerotic lesions develop. 2 The only extensive studies of intimal formation are in the ductus arteriosus. 3–5 Of course, the ductus is not a site that develops atherosclerosis. The only atherosclerosis-prone intima reported on before the present study is the left anterior descending carotid artery. 6