title: Cathepsin K deficiency reduces elastase perfusion-induced abdominal aortic aneurysms in mice.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Jiusong
authors.initials: J
authors.lastname: Sun
authors.forename: Galina K
authors.initials: GK
authors.lastname: Sukhova
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.forename: Sara
authors.initials: S
authors.lastname: Sjöberg
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.forename: Mingcan
authors.initials: M
authors.lastname: Xia
authors.forename: Na
authors.initials: N
authors.lastname: Xiong
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Gelb
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shi
mesh_terms: D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D056657:Cathepsin K / Q000172:deficiency* / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D018919:Neovascularization, Physiologic; D010196:Pancreatic Elastase / Q000008:administration & dosage
chemical_list: D004549:Elastin; D010196:Pancreatic Elastase; D056657:Cathepsin K; C534132:Ctsk protein, mouse