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dc.contributor.authorSon, B. K.-
dc.contributor.authorSawaki, D.-
dc.contributor.authorTomida, S.-
dc.contributor.authorFujita, D.-
dc.contributor.authorAizawa, K.-
dc.contributor.authorAoki, H.-
dc.contributor.authorAkishita, M.-
dc.contributor.authorManabe, I.-
dc.contributor.authorKomuro, I.-
dc.contributor.authorFriedman, S. L.-
dc.contributor.authorNagai, R.-
dc.contributor.authorSuzuki, Toru-
dc.identifier.citationNature Communications, 2015, 6:6994en
dc.descriptionSupplementary Information is available via doi:10.1038/ncomms7994en
dc.description.abstractAortic 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.en
dc.description.sponsorshipThis research was funded in part by the Ministry of Health, Labour and Welfare of Japan; Grants-in Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the Japan Society for the Promotion of Science through its Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program). This study was also supported by the National Institutes of Health National Cancer Institute (DK37340).en
dc.publisherNature Publishing Groupen
dc.rightsArchived with reference to SHERPA/RoMEO and publisher website.en
dc.titleGranulocyte macrophage colony-stimulating factor is required for aortic dissection/intramural haematoma.en
dc.typeJournal Articleen
dc.type.subtypeJournal Article-
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicineen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cardiovascular Sciencesen
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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