Schematic representation of NF-κB as an integrator in atherogenesis. Many of the diverse agents associated with the onset of lesion formation interact with specific receptors. Angiotensin II (Ang II), cytokines, advanced glycosylation end products (AGEs), or oxidized lipids bind to the Ang II receptor (AT1), cytokine receptors, the receptor for AGEs (RAGE), or the scavenger receptor (SR), respectively. LPS interacts with a complex of LPS-binding protein (LBP), CD14 and a toll-like receptor (TLR). The mechanisms by which hemodynamic forces are perceived by vascular cells are only partially appreciated, but may involve specific receptors or links between the cytoskeleton, integrins, and ECM. Ligand binding by most of these receptors results in recruitment of adaptor proteins and activation of intermediate kinases (not shown). These events ultimately lead to the activation of an IKK complex. The best characterized kinase complex consists of IKK-α, IKK-β, and the structural component IKK-γ, although other similar complexes may exist. The activated IKK complex specifically phosphorylates the IκBs, which then undergo a rapid polyubiquitination process prior to degradation by the proteosome. Following release from the inhibitor, NF-κB dimers translocate from the cytoplasm to the nucleus, where they bind target genes and stimulate transcription of specific sets of genes relevant to the pathophysiology of the vessel wall.