2013 Fiscal Year Final Research Report
Novel mechanism of aortic aneurysm/dissection involving regulation of inflammatory cytokines
| Project/Area Number |
24790737
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SON Bokyung 東京大学, 医学部附属病院, 特任研究員 (20625256)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 大動脈瘤・解離 / 慢性炎症 / GM-CSF / KLF6 |
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| Research Abstract |
Aortic dissection is a fatal disease caused by catastrophic separation of the aortic wall. The underlying mechanisms of the condition remain unclear. Here we show that granulocyte macrophage colony-stimulating factor (GM-CSF) is a triggering mechanism for this condition.
Perturbation of the GM-CSF response with highly increased levels of this cytokine were seen in a murine model of aortic dissection that we developed using transcription factor Kruppel-like factor 6 (KLF6)-myeloid-specific conditional deficient mice with aortic inflammation. Mechanistically, KLF6 regulated both expression and secretion of GM-CSF.
Intriguingly, administration of neutralizing antibody against GM-CSF prevented the condition in these mice. Conversely, administration of GM-CSF in combination with aortic inflammation to wild-type mice was sufficient to induce aortic dissection suggesting GM-CSF is a key regulatory molecule causative of aortic dissection.
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