Dendritic cells (green) are abundant in atherosclerosis-prone vessel regions.

Atherosclerotic lesions are initiated mostly at vessel branch points and curvatures, where blood flow is irregular and inflammatory gene expression is high. Circulating blood cells—including macrophages, T cells, and dendritic cells (DCs)—accumulate in these areas at steady state, creating a scaffold on which the lesion is built. On page 2073, Jongstra-Bilen et al. suggest that it is DC build-up that most portends future lesion development.

Although many cell types have been shown to congregate in lesion-prone regions of vessels, few studies have analyzed the relative abundance of these cell types in lesion-prone and lesion-resistant regions. Nor have they compared the cellular composition in atherosclerosis-susceptible and -resistant strains of mice.

Jongstra-Bilen and colleagues now show that, in normal mice, DCs (but not T cells) were 100 times more abundant in lesion-prone areas of the aorta than in resistant areas. But these cells were found only in the innermost vessel layer (the intima). In the outermost layer (the adventitia), the cellular composition (mostly macrophages and T cells) was comparable in lesion-prone and -resistant regions.

These strategically located DCs were more plentiful in atherosclerosis-prone mice than in resistant mice, suggesting that a preponderance of intimal DCs might predispose them toward atherosclerosis. The authors speculate that the dcs, which are adept at gobbling up macromolecules, might take up oxidized lipoproteins. Lipid-laden macrophages are important building blocks of atherosclerotic plaques—but perhaps these cells get in on the act only after lipid-stuffed DCs set the foundation.