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dc.contributor.authorSun, Jiusong
dc.contributor.authorSukhova, Galina K.
dc.contributor.authorZhang, Jie
dc.contributor.authorChen, Han
dc.contributor.authorSjoberg, Sara
dc.contributor.authorLibby, Peter
dc.contributor.authorXia, Mingcan
dc.contributor.authorXiong, Na
dc.contributor.authorGelb, Bruce D.
dc.contributor.authorShi, Guo-Ping
dc.date.accessioned2018-01-24T18:02:03Z
dc.date.issued2011
dc.identifier.citationSun, J., G. K. Sukhova, J. Zhang, H. Chen, S. Sjoberg, P. Libby, M. Xia, N. Xiong, B. D. Gelb, and G.-P. Shi. 2011. “Cathepsin K Deficiency Reduces Elastase Perfusion-Induced Abdominal Aortic Aneurysms in Mice.” Arteriosclerosis, Thrombosis, and Vascular Biology 32 (1) (August 4): 15–23. doi:10.1161/atvbaha.111.235002.en_US
dc.identifier.issn1079-5642en_US
dc.identifier.issn1524-4636en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:34728622
dc.description.abstractObjective: Cathepsin K (CatK) is one of the most potent mammalian elastases. We have previously shown increased expression of CatK in human abdominal aortic aneurysm (AAA) lesions. Whether this protease participates directly in AAA formation, however, remains unknown. Methods and Results: Mouse experimental AAA was induced with aortic perfusion of a porcine pancreatic elastase. Using this experimental model, we demonstrated that absence of CatK prevented AAA formation in mice 14 days postperfusion. CatK deficiency significantly reduced lesion CD4 T-cell content, total lesion and medial cell proliferation and apoptosis, medial smooth muscle cell (SMC) loss, elastinolytic CatL and CatS expression, and elastin fragmentation, but it did not affect AAA lesion Mac-3 macrophage accumulation or CD31 microvessel numbers. In vitro studies revealed that CatK contributed importantly to CD4 T-cell proliferation, SMC apoptosis, and other cysteinyl cathepsin and matrix metalloproteinase expression and activities in SMCs and endothelial cells but played negligible roles in microvessel growth and monocyte migration. AAA lesions from CatK-deficient mice showed reduced elastinolytic cathepsin activities compared with those from wild-type control mice. Conclusion: This study demonstrates that CatK plays an essential role in AAA formation by promoting T-cell proliferation, vascular SMC apoptosis, and elastin degradation and by affecting vascular cell protease expression and activities.en_US
dc.description.sponsorshipOther Research Uniten_US
dc.language.isoen_USen_US
dc.publisherOvid Technologies (Wolters Kluwer Health)en_US
dc.relation.isversionofdoi:10.1161/ATVBAHA.111.235002en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pubmed/21817099en_US
dash.licenseMETA_ONLY
dc.subjectaneurysmsen_US
dc.subjectcathepsin Ken_US
dc.subjectelastaseen_US
dc.subjectsmooth muscle cellen_US
dc.subjectT cellen_US
dc.titleCathepsin K Deficiency Reduces Elastase Perfusion-Induced Abdominal Aortic Aneurysms in Miceen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalArteriosclerosis, Thrombosis, and Vascular Biologyen_US
dash.depositing.authorLibby, Peter
dash.embargo.until10000-01-01
dc.identifier.doi10.1161/ATVBAHA.111.235002*
workflow.legacycommentsauth.collection Move to HMS oap.needman (MM)en_US
dash.contributor.affiliatedXia, Mingcan
dash.contributor.affiliatedSukhova, Galina
dash.contributor.affiliatedSun, Jiusong
dash.contributor.affiliatedZhang, Jie
dash.contributor.affiliatedChen, Han
dash.contributor.affiliatedShi, Guo-Ping
dash.contributor.affiliatedLibby, Peter
dc.identifier.orcid0000-0002-1502-502X


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