Please use this identifier to cite or link to this item:
Title: Granulocyte macrophage colony-stimulating factor is required for aortic dissection/intramural haematoma.
Authors: Son, B. K.
Sawaki, D.
Tomida, S.
Fujita, D.
Aizawa, K.
Aoki, H.
Akishita, M.
Manabe, I.
Komuro, I.
Friedman, S. L.
Nagai, R.
Suzuki, Toru
First Published: 29-Apr-2015
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.
DOI Link: 10.1038/ncomms7994
eISSN: 2041-1723
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
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

Files in This Item:
File Description SizeFormat 
41328_3_merged_1427118290.pdfPost-review (final submitted)1.29 MBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.