Targeting activation of specific NF-κB subunits prevents stress-dependent atherothrombotic gene expression.

Zdenka Djuric*, Muhammed Kashif, Thomas Fleming, Sajjad Muhammad, David Piel, Rüdiger von Bauer, Florian Bea, Stephan Herzig, Martin Zeier, Marina Pizzi, Berend Isermann, Markus Hecker, Markus Schwaninger, Angelika Bierhaus, Peter P. Nawroth

*Corresponding author for this work
6 Citations (Scopus)


Psychosocial stress has been shown to be a contributing factor in the development of atherosclerosis. Although the underlying mechanisms have not been elucidated entirely, it has been shown previously that the transcription factor nuclear factor-κB (NF-κB) is an important component of stress-activated signaling pathway. In this study, we aimed to decipher the mechanisms of stress-induced NF-κB-mediated gene expression, using an in vitro and in vivo model of psychosocial stress. Induction of stress led to NF-κB-dependent expression of proinflammatory (tissue factor, intracellular adhesive molecule 1 [ICAM-1]) and protective genes (manganese superoxide dismutase [MnSOD]) via p50, p65 or cRel. Selective inhibition of the different subunits and the respective kinases showed that inhibition of cRel leads to the reduction of atherosclerotic lesions in apolipoprotein(-/-) (ApoE(-/-)) mice via suppression of proinflammatory gene expression. This observation may therefore provide a possible explanation for ineffectiveness of antioxidant therapies and suggests that selective targeting of cRel activation may provide a novel approach for the treatment of stress-related inflammatory vascular disease.

Original languageEnglish
JournalMolecular medicine (Cambridge, Mass.)
Pages (from-to)1375-1386
Number of pages12
Publication statusPublished - 01.12.2012


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