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Mol Med. 2012 Dec 20;18:1375-86. doi: 10.2119/molmed.2012.00282.

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

Author information

1
Department of Medicine I and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany.

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.

PMID:
23114885
PMCID:
PMC3533647
DOI:
10.2119/molmed.2012.00282
[Indexed for MEDLINE]
Free PMC Article

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