Nck1 is a critical adaptor between proatherogenic blood flow, inflammation, and atherosclerosis.

Atherosclerosis is an inflammatory condition of the arteries that has profound incidence and increasing prevalence. Although endothelial cells detect changes in blood flow, how endothelial activation contributes to atherogenic inflammation is not well understood. In this issue of the JCI, Alfaidi et al. used mouse models to explore flow-induced endothelial activation. The authors revealed a role for Nck1 and a specific activator of the innate immune response, the downstream interleukin receptor-associated kinase-1 (IRAK-1) in NF-κB-mediated inflammation and atherosclerosis susceptibility. These results link disturbed blood flow to NF-κB-mediated inflammation, which promotes atherosclerosis, and provide Nck1 as a potential target for the treatment of atherosclerosis.