The critical departure from previous studies comes when Trigueros-Motos et al16 address the question of whether differences in SMC identity conferred by origin and position in development translate into aortic segment–specific differences in responses to proinflammatory stimuli involved in the progression of vascular disease in adults. Here, the key findings are that both basal and tumor necrosis factor α–stimulated nuclear factor (NF)-κB activation and binding to DNA were significantly greater in SMCs from atherosclerosis-prone AAo segments compared with SMCs from atherosclerosis-resistant TAo segments. Moreover, when one particular member of the Hox groups 6 to 9, that is, HOXA9, was examined in detail, it was found that high levels of NF-κB activity strongly repress HOXA9 expression and, in reciprocal fashion, HOXA9 expression can repress NF-κB transcriptional activity (Figure). These data have exciting implications for a better understanding of the segment-specific distribution of atherosclerosis in the arterial system reported by DeBakey and Glaeser. 1 They raise the possibility that atherosclerosis-prone versus atherosclerosisresistant aortic segments exhibit differential responses to a common level of inflammatory cytokines, in part, as a consequence of stable differences in SMC identity conferred by differences in the topographical position of their progenitors during development. Although the molecular mechanisms that write these stable differences to the SMC epigenome during development are not yet understood, the consequences of these mechanisms may be to produce a mosaic pattern of susceptibility on which the more familiar stimuli of arterial injury, inflammation, and thrombosis act to produce overt vascular disease. 20, 21