title: Nuclear factor kappa B signaling in macrophage function and atherogenesis.
abstract: OBJECTIVE
  Atherosclerosis is a chronic inflammatory disease of the medium and large-sized arteries. Nuclear factor kappaB transcription factors are major regulators of inflammatory responses, and aberrant nuclear factor kappaB regulation is linked to a large number of diseases. Focusing on macrophages, this review will discuss recent literature on the role of nuclear factor kappaB and the signaling pathways regulating its activity in atherosclerosis.
  
  
  RESULTS
  After the initial identification of activated nuclear factor kappaB in human atherosclerotic lesions, the involvement of this family of transcription factors in atherogenesis has gained growing attention. It is now clear that signaling pathways activating nuclear factor kappaB, and nuclear factor kappaB action, constitute major players at all stages of the atherosclerotic process. Long considered a pro-atherogenic factor, recent studies indicate that the actual role of nuclear factor kappaB might prove to be far more complex. Apart from activating many pro-inflammatory genes linked to atherogenesis, nuclear factor kappaB regulates cellular processes such as cell survival and proliferation. In addition, its important role in inflammatory resolution and anti-inflammatory gene transcription suggests that its activation at different cell types or different stages of the atherosclerotic process might have distinct and opposing results.
  
  
  CONCLUSIONS
  The numerous diseases in which aberrant nuclear factor kappaB action is found to play a crucial role makes it an intensively studied target for drug interventions. However, given its pleiotropic functions in inflammation and immunity, a more targeted modulation of its activity, at a cell type-specific or disease stage-specific level, could provide safer therapeutic solutions.
authors.affiliation: Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
authors.forename: Sofia
authors.initials: S
authors.lastname: Xanthoulea
authors.forename: Danielle M J
authors.initials: DM
authors.lastname: Curfs
authors.forename: Marten H
authors.initials: MH
authors.lastname: Hofker
authors.forename: Menno P J
authors.initials: MP
authors.lastname: de Winther
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D016328:NF-kappa B / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D018836:Inflammation Mediators; D016328:NF-kappa B