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dc.contributor.authorShi, Guo-Ping
dc.contributor.authorSukhova, Galina K.
dc.contributor.authorGrubb, Anders
dc.contributor.authorDucharme, Anique
dc.contributor.authorRhode, Luis H.
dc.contributor.authorLee, Richard Theodore
dc.contributor.authorRidker, Paul M.
dc.contributor.authorLibby, Peter
dc.contributor.authorChapman, Harold A.
dc.date.accessioned2014-12-12T20:31:31Z
dc.date.issued1999
dc.identifier.citationShi, Guo-Ping, Galina K. Sukhova, Anders Grubb, Anique Ducharme, Luis H. Rhode, Richard T. Lee, Paul M. Ridker, Peter Libby, and Harold A. Chapman. 1999. “Cystatin C Deficiency in Human Atherosclerosis and Aortic Aneurysms.” J. Clin. Invest. 104 (9) (November 1): 1191–1197. doi:10.1172/jci7709.en_US
dc.identifier.issn0021-9738en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13506934
dc.description.abstractThe pathogenesis of atherosclerosis and abdominal aortic aneurysm involves breakdown of the elastic laminae. Elastolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage, but whether endogenous local inhibitors counterbalance these proteases is unknown. We show here that, whereas cystatin C is normally expressed in vascular wall smooth muscle cells (SMCs), this cysteine protease inhibitor is severely reduced in both atherosclerotic and aneurysmal aortic lesions. Furthermore, increased abdominal aortic diameter among 122 patients screened by ultrasonography correlated inversely with serum cystatin C levels. In vitro, cytokine-stimulated vascular SMCs secrete cathepsins, whose elastolytic activity could be blocked when cystatin C secretion was induced by treatment with TGF-β1. The findings highlight a potentially important role for imbalance between cysteine proteases and cystatin C in arterial wall remodeling and establish that cystatin C deficiency occurs in vascular disease.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.relation.isversionofdoi:10.1172/JCI7709en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC409823/en_US
dash.licenseLAA
dc.titleCystatin C deficiency in human atherosclerosis and aortic aneurysmsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalJournal of Clinical Investigationen_US
dash.depositing.authorLibby, Peter
dc.date.available2014-12-12T20:31:31Z
dc.identifier.doi10.1172/JCI7709*
dash.contributor.affiliatedSukhova, Galina
dash.contributor.affiliatedLee, Richard
dash.contributor.affiliatedShi, Guo-Ping
dash.contributor.affiliatedLibby, Peter
dash.contributor.affiliatedRidker, Paul
dc.identifier.orcid0000-0002-1502-502X
dc.identifier.orcid0000-0003-1249-4522


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