Granulocyte macrophage colony-stimulating factor is required for aortic dissection/intramural haematoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Bo-Kyung Son, Daigo Sawaki, Shota Tomida, Daishi Fujita, Kenichi Aizawa, Hiroki Aoki, Masahiro Akishita, Ichiro Manabe, Issei Komuro, Scott L. Friedman, Ryozo Nagai, Toru Suzuki

ABSTRACT

Aortic dissection and intramural haematoma comprise an aortopathy involving separation of the aortic wall. Underlying mechanisms of the condition remain unclear. Here we show that granulocyte macrophage colony-stimulating factor (GM-CSF) is a triggering molecule for this condition. Transcription factor Krüppel-like factor 6 (KLF6)-myeloid-specific conditional deficient mice exhibit this aortic phenotype when subjected to aortic inflammation. Mechanistically, KLF6 downregulates expression and secretion of GM-CSF. Administration of neutralizing antibody against GM-CSF prevents the condition in these mice. Conversely, administration of GM-CSF in combination with aortic inflammation to wild-type mice is sufficient to induce the phenotype, suggesting the general nature of effects. Moreover, patients with this condition show highly increased circulating levels of GM-CSF, which is also locally expressed in the dissected aorta. GM-CSF is therefore a key regulatory molecule causative of this aortopathy, and modulation of this cytokine might be an exploitable treatment strategy for the condition. More... »

PAGES

6994

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms7994

DOI

http://dx.doi.org/10.1038/ncomms7994

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012188139

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25923510


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