Cathepsin L Activity Is Essential to Elastase Perfusion-Induced Abdominal Aortic Aneurysms in Mice

DSpace/Manakin Repository

Cathepsin L Activity Is Essential to Elastase Perfusion-Induced Abdominal Aortic Aneurysms in Mice

Citable link to this page

 

 
Title: Cathepsin L Activity Is Essential to Elastase Perfusion-Induced Abdominal Aortic Aneurysms in Mice
Author: Sun, Jiusong; Sukhova, Galina K.; Zhang, Jie; Chen, Han; Sjoberg, S.; Libby, Peter; Xiang, M.; Wang, J.; Peters, C.; Reinheckel, T.; Shi, Guo-Ping

Note: Order does not necessarily reflect citation order of authors.

Citation: Sun, J., G. K. Sukhova, J. Zhang, H. Chen, S. Sjoberg, P. Libby, M. Xiang, et al. 2011. “Cathepsin L Activity Is Essential to Elastase Perfusion-Induced Abdominal Aortic Aneurysms in Mice.” Arteriosclerosis, Thrombosis, and Vascular Biology 31 (11) (August 25): 2500–2508. doi:10.1161/atvbaha.111.230201.
Access Status: Full text of the requested work is not available in DASH at this time (“dark deposit”). For more information on dark deposits, see our FAQ.
Full Text & Related Files:
Abstract: Objective—The development of abdominal aortic aneurysms (AAA) requires extensive aortic wall matrix degradation. Human AAA lesions express high levels of cathepsin L (CatL), one of the most potent mammalian elastases. Whether this protease participates directly in AAA pathogenesis, however, is unknown.

Methods and Results—We generated experimental AAA with aortic elastase perfusion in mice and established an essential role of CatL in AAA formation. After 14 days postperfusion, most wild-type (Ctsl+/+) mice developed AAA, but none of the CatL-deficient (Ctsl−/−) mice did. AAA lesion macrophage contents, CD4+ T cell numbers, CD31+ and laminin-5 angiogenic fragment γ2+ microvessel numbers, and elastin fragmentation were all significantly lower in Ctsl−/− mice than in Ctsl+/+ mice. While lesions from Ctsl−/− mice contained fewer Ki67+ proliferating cells than did Ctsl+/+ mice, the absence of CatL did not affect lesion apoptotic cell contents or medial smooth-muscle cell loss significantly. Mechanistic studies indicated that the absence of CatL reduced lesion chemokine monocyte chemotactic protein-1 content, macrophage and T-cell in vitro transmigration, and angiogenesis, and altered the expression and activities of matrix metalloproteinases and other cysteinyl cathepsins in inflammatory cells, vascular cells, and AAA lesions.

Conclusion—CatL contributes to AAA formation by promoting lesion inflammatory cell accumulation, angiogenesis, and protease expression.
Published Version: doi:10.1161/ATVBAHA.111.230201
Other Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312037/
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:32605692
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters