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

Research output: Contribution to journalArticlepeer-review

Abstract

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
Pages (from-to)1375-1386
Number of pages12
JournalMolecular medicine (Cambridge, Mass.)
Volume18
Publication statusPublished - 2012

ASJC Scopus subject areas

  • Medicine(all)

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