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dc.contributor.authorSun, Jiusong
dc.contributor.authorSukhova, Galina K.
dc.contributor.authorYang, Min
dc.contributor.authorWolters, Paul J.
dc.contributor.authorMacFarlane, Lindsey Adair
dc.contributor.authorLibby, Peter
dc.contributor.authorSun, Chongxiu
dc.contributor.authorZhang, Yadong
dc.contributor.authorLiu, Jianming
dc.contributor.authorEnnis, Terri L.
dc.contributor.authorKnispel, Rebecca
dc.contributor.authorXiong, Wanfen
dc.contributor.authorThompson, Robert W.
dc.contributor.authorBaxter, B. Timothy
dc.contributor.authorShi, Guo-Ping
dc.date.accessioned2014-12-12T20:47:43Z
dc.date.issued2007
dc.identifier.citationSun, Jiusong, Galina K. Sukhova, Min Yang, Paul J. Wolters, Lindsey A. MacFarlane, Peter Libby, Chongxiu Sun, et al. 2007. “Mast Cells Modulate the Pathogenesis of Elastase-Induced Abdominal Aortic Aneurysms in Mice.” J. Clin. Invest. 117 (11) (November 1): 3359–3368. doi:10.1172/jci31311.en_US
dc.identifier.issn0021-9738en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13506937
dc.description.abstractAbdominal aortic aneurysm (AAA), an inflammatory disease, involves leukocyte recruitment, immune responses, inflammatory cytokine production, vascular remodeling, neovascularization, and vascular cell apoptosis, all of which contribute to aortic dilatation. This study demonstrates that mast cells, key participants in human allergic immunity, participate in AAA pathogenesis in mice. Mast cells were found to accumulate in murine AAA lesions. Mast cell–deficient KitW-sh/KitW-sh mice failed to develop AAA elicited by elastase perfusion or periaortic chemical injury. KitW-sh/KitW-sh mice had reduced aortic expansion and internal elastic lamina degradation; decreased numbers of macrophages, CD3+ T lymphocytes, SMCs, apoptotic cells, and CD31+ microvessels; and decreased levels of aortic tissue IL-6 and IFN-γ. Activation of mast cells in WT mice via C48/80 injection resulted in enhanced AAA growth while mast cell stabilization with disodium cromoglycate diminished AAA formation. Mechanistic studies demonstrated that mast cells participated in angiogenesis, aortic SMC apoptosis, and matrix-degrading protease expression. Reconstitution of KitW-sh/KitW-sh mice with bone marrow–derived mast cells from WT or TNF-α–/– mice, but not from IL-6–/– or IFN-γ–/– mice, caused susceptibility to AAA formation to be regained. These results demonstrate that mast cells participate in AAA pathogenesis in mice by releasing proinflammatory cytokines IL-6 and IFN-γ, which may induce aortic SMC apoptosis, matrix-degrading protease expression, and vascular wall remodeling, important hallmarks of arterial aneurysms.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.relation.isversionofdoi:10.1172/JCI31311en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pubmed/17932568en_US
dash.licenseLAA
dc.titleMast cells modulate the pathogenesis of elastase-induced abdominal aortic aneurysms in miceen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalJournal of Clinical Investigationen_US
dash.depositing.authorLibby, Peter
dc.date.available2014-12-12T20:47:43Z
dc.identifier.doi10.1172/JCI31311*
dash.authorsorderedfalse
dash.contributor.affiliatedMacFarlane, Lindsey
dash.contributor.affiliatedLiu, Jianming
dash.contributor.affiliatedSukhova, Galina
dash.contributor.affiliatedSun, Jiusong
dash.contributor.affiliatedShi, Guo-Ping
dash.contributor.affiliatedLibby, Peter
dc.identifier.orcid0000-0002-1502-502X


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