| First Author | Son BK | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6994 | PubMed ID | 25923510 |
| Mgi Jnum | J:222781 | Mgi Id | MGI:5645596 |
| Doi | 10.1038/ncomms7994 | Citation | Son BK, et al. (2015) Granulocyte macrophage colony-stimulating factor is required for aortic dissection/intramural haematoma. Nat Commun 6:6994 |
| abstractText | 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 Kruppel-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. |
