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Review
. 2001 Feb;107(3):255-64.
doi: 10.1172/JCI10373.

NF-kappaB: pivotal mediator or innocent bystander in atherogenesis?

T Collins  1 , M I Cybulsky
Affiliations
Review

NF-kappaB: pivotal mediator or innocent bystander in atherogenesis?

T Collins et al. J Clin Invest. 2001 Feb.
No abstract available

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Figures

Figure 1
Figure 1
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.
Figure 2
Figure 2
NF-κB and hemodynamics in regions predisposed and protected from atherosclerosis. Schematic of hemodynamics in the human carotid bifurcation. The straight segment of the artery proximal to the bifurcation is typical of regions resistant to atherogenesis (left). These regions are associated with a uniformly laminar blood flow profile that may induce the expression of various classes of atheroprotective genes. Examples of each class from the work of Akimoto et al. (46) and Gimbrone and coworkers (42) are shown (below left). It is not known whether this class of genes is coordinately regulated. In contrast, disturbed laminar flow, with boundary layer separation, flow reversal, secondary flows, and shifting stagnation points, is typical of regions predisposed to atherosclerosis (right). In these regions, the mean shear stress is relatively low and the NF-κB signal transduction pathway may be primed for activation. Systemic risk factors would therefore preferentially induce the expression of proatherogenic NF-κB–dependent genes at lesion-predisposed sites. Examples of each class are provided (below right).
See this image and copyright information in PMC

References

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