Figure 2

In this model, atherosclerosis process results from pathophysiological activity of UPS that may activate the NFkB inflammatory activity in the plaque macrophages. Activation pathway of NFkB, a homo- or heterodimeric transcription factor, composed by members of the Rel family of proteins. The classical example of NFkB is the heterodimer of p50 and p65, which binds to the 5'-GGGANNYYCCC-3' consensus sequence, once released from the association with an inhibitory molecule of the IkB family, primarily IkBα and IkBβ. Upon exposure of the cell to various stimuli such as increase in oxidative stress, two specific serine residues are rapidly phosphorylated by the IKK1/2 kinases. Once phosphorylated, IkBs undergo degradation via the ubiquitin-proteasome pathway in this main route of NFkB activation.