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http://purl.uniprot.org/citations/21350211http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21350211http://www.w3.org/2000/01/rdf-schema#comment"

Rationale

The nuclear factor (NF)-κB pathway is involved in arterial inflammation. Although the signaling pathways that regulate transcriptional activation of NF-κB are defined, the mechanisms that regulate the expression levels of NF-κB transcription factors are uncertain.

Objective

We studied the signaling mechanisms that regulate RelA NF-κB subunit expression in endothelial cells (ECs) and their role in arterial inflammation.

Methods and results

Gene silencing and chromatin immunoprecipitation revealed that RelA expression was positively regulated by c-Jun N-terminal kinase (JNK) and the downstream transcription factor ATF2 in ECs. We concluded that this pathway promotes focal arterial inflammation as genetic deletion of JNK1 reduced NF-κB expression and macrophage accumulation at an atherosusceptible site. We hypothesized that JNK signaling to NF-κB may be controlled by mechanical forces because atherosusceptibility is associated with exposure to disturbed blood flow. This was assessed by positron emission tomography imaging of carotid arteries modified with a constrictive cuff, a method that was developed to study the effects of disturbed flow on vascular physiology in vivo. This approach coupled to en face staining revealed that disturbed flow elevates NF-κB expression and inflammation in murine carotid arteries via JNK1.

Conclusions

We demonstrate that disturbed blood flow promotes arterial inflammation by inducing NF-κB expression in endothelial cells via JNK-ATF2 signaling. Thus, our findings illuminate a novel form of JNK-NF-κB crosstalk that may determine the focal nature of arterial inflammation and atherosclerosis."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.org/dc/terms/identifier"doi:10.1161/circresaha.110.233841"xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Jones H."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Khalil M."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Haskard D.O."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Chaudhury H."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Evans P.C."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Mason J.C."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Zakkar M."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Udalova I."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Krams R."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Luong l.e. A."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Van der Heiden K."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Gsell W."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Saliba D."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Cuhlmann S."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/author"Tremoleda J.L."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/name"Circ Res"xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/pages"950-959"xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/title"Disturbed blood flow induces RelA expression via c-Jun N-terminal kinase 1: a novel mode of NF-kappaB regulation that promotes arterial inflammation."xsd:string
http://purl.uniprot.org/citations/21350211http://purl.uniprot.org/core/volume"108"xsd:string
http://purl.uniprot.org/citations/21350211http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21350211
http://purl.uniprot.org/citations/21350211http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21350211