NF-κB signaling at the crossroads of inflammation and atherogenesis: searching for new therapeutic links

Expert Opin Ther Targets. 2014 Sep;18(9):1089-101. doi: 10.1517/14728222.2014.938051. Epub 2014 Jul 8.

Abstract

Introduction: NF-κB is a protein complex acting as a primary transcription factor and fast messenger to harmful cellular stimuli, including inflammation. Carotid atherosclerosis is an inflammatory process leading to atheroma formation and ultimately complicating the patient's condition. This review aims to critically summarize the role of NF-κB in atheroma formation and evolution, also highlighting its potential therapeutic utility.

Areas covered: This literature review presents the most recent data in terms of NF-κB, atherosclerosis and implicating factors, with special focus on the carotid artery setting. Results are categorized according to atheroma stage and are discussed for each one respectively, forming an NF-κB mediated atherosclerosis evolvement model per stage. Targeting NF-κB by inhibitors or enhancers and their potential effectiveness are also discussed.

Expert opinion: The current data suggest that NF-κB plays a critical role in all stages of plaque evolution toward complexity, implicating genes, membrane and cellular proteins, polypeptides, chemokines and hormones. It also seems capable of assisting several pharmaceutical agents, unfolding either directly or indirectly their anti-inflammatory/anti-atherogenic properties. Targeting NF-κB signaling by specific inhibitors or enhancers may provide new therapeutic strategies against atherogenic inflammatory process.

Keywords: NF-κB inhibitors/enhancers; NF-κB signaling; atherosclerosis pathophysiology; carotid plague evolution stages; inflammation.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Atherosclerosis / drug therapy
  • Atherosclerosis / physiopathology*
  • Carotid Artery Diseases / drug therapy
  • Carotid Artery Diseases / physiopathology
  • Drug Design
  • Humans
  • Inflammation / drug therapy
  • Inflammation / physiopathology
  • Molecular Targeted Therapy
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism*
  • Plaque, Atherosclerotic / drug therapy
  • Plaque, Atherosclerotic / physiopathology*
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • NF-kappa B