ECM controls flow-induced NF-κB

Orr et al. (page 191) show that the composition of the subendothelial extracellular matrix (ECM) controls whether NF-κB, a major inflammatory response protein, is activated by fluid shear stress.Atherosclerosis typically occurs in regions of disturbed blood flow, such as vascular branch points. Integrins become activated in response to increased flow, converting the proteins to a high-affinity conformation. Once activated, integrins bind to the subendothelial ECM and initiate intracellular signaling. Additionally, the binding of some integrins, but not all, triggers NF-κB signaling. Others have observed that NF-κB signaling in the endothelium contributes to the initiation of atherosclerosis. Now, Orr et al. have connected these observations.

In an in vitro system, they found that NF-κB was activated in response to flow when cells were plated on fibronectin or fibrinogen, which are associated with damage or inflammation, but...