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|Title:||Granulocyte macrophage colony-stimulating factor is required for aortic dissection/intramural haematoma.|
|Authors:||Son, B. K.|
Friedman, S. L.
|Publisher:||Nature Publishing Group|
|Citation:||Nature Communications, 2015, 6:6994|
|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.|
|Rights:||Archived with reference to SHERPA/RoMEO and publisher website.|
|Description:||Supplementary Information is available via doi:10.1038/ncomms7994|
|Appears in Collections:||Published Articles, Dept. of Cardiovascular Sciences|
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