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dc.contributor.authorSukhova, Galina K.
dc.contributor.authorShi, Guo-Ping
dc.contributor.authorSimon, D I
dc.contributor.authorChapman, H A
dc.contributor.authorLibby, Peter
dc.date.accessioned2014-12-12T17:46:39Z
dc.date.issued1998
dc.identifier.citationSukhova, G K, G P Shi, D I Simon, H A Chapman, and P Libby. 1998. “Expression of the Elastolytic Cathepsins S and K in Human Atheroma and Regulation of Their Production in Smooth Muscle Cells.” J. Clin. Invest. 102 (3) (August 1): 576–583. doi:10.1172/jci181. http://dx.doi.org/10.1172/JCI181.en_US
dc.identifier.issn0021-9738en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13506487
dc.description.abstractFormation of the atherosclerotic intima must involve altered metabolism of the elastin-rich arterial extracellular matrix. Proteases potentially involved in these processes remain unclear. This study examined the expression of the potent elastases cathepsins S and K in human atheroma. Normal arteries contained little or no cathepsin K or S. In contrast, macrophages in atheroma contained abundant immunoreactive cathepsins K and S. Intimal smooth muscle cells (SMC), especially cells appearing to traverse the internal elastic laminae, also contained these enzymes. Extracts of atheromatous tissues had approximately twofold greater elastase-specific activity than extracts of uninvolved arteries, mostly due to cysteine proteases. Cultured human SMC displayed no immunoreactive cathepsins K and S and exhibited little or no elastolytic activity when incubated with insoluble elastin. SMC stimulated with the atheroma-associated cytokines IL-1beta or IFN-gamma secreted active cathepsin S and degraded substantial insoluble elastin (15-20 microg/10(6) cells/24 h). A selective inhibitor of cathepsin S blocked > 80% of this elastolytic activity. The presence of cathepsins K and S at sites of vascular matrix remodeling and the ability of SMC and macrophages to use these enzymes to degrade elastin supports a role for elastolytic cathepsins in vessel wall remodeling and identifies novel therapeutic targets in regulating plaque stability.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.relation.isversionofdoi:10.1172/JCI181en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC508918/en_US
dash.licenseLAA
dc.subjectatherosclerosisen_US
dc.subjectcysteine proteaseen_US
dc.subjectsmooth muscle cellen_US
dc.subjectelastolytic activityen_US
dc.titleExpression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cellsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalJournal of Clinical Investigationen_US
dash.depositing.authorLibby, Peter
dc.date.available2014-12-12T17:46:39Z
dc.identifier.doi10.1172/JCI181*
dash.contributor.affiliatedSukhova, Galina
dash.contributor.affiliatedShi, Guo-Ping
dash.contributor.affiliatedLibby, Peter
dc.identifier.orcid0000-0002-1502-502X


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