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

Bo-Kyung Son, Daigo Sawaki, Shota Tomida, Daishi Fujita, Kenichi Aizawa, Hiroki Aoki, Masahiro Akishita, Ichiro Manabe, Issei Komuro, Scott L. Friedman, Ryozo Nagai and Toru Suzuki ()
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Bo-Kyung Son: Graduate School of Medicine, The University of Tokyo
Daigo Sawaki: Graduate School of Medicine, The University of Tokyo
Shota Tomida: Graduate School of Medicine, The University of Tokyo
Daishi Fujita: Graduate School of Medicine, The University of Tokyo
Kenichi Aizawa: Graduate School of Medicine, The University of Tokyo
Hiroki Aoki: Cardiovascular Research Institute, Kurume University
Masahiro Akishita: Graduate School of Medicine, The University of Tokyo
Ichiro Manabe: Graduate School of Medicine, The University of Tokyo
Issei Komuro: Graduate School of Medicine, The University of Tokyo
Scott L. Friedman: Icahn School of Medicine at Mount Sinai
Ryozo Nagai: Jichi Medical University
Toru Suzuki: Graduate School of Medicine, The University of Tokyo

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7994

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