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Cathepsin S Contributes to Macrophage Migration via Degradation of Elastic Fiber Integrity to Facilitate Vein Graft Neointimal Hyperplasia.
MedLine Citation:
PMID:  24319016     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: Cathepsin S (Cat S) is a potent lysosomal protease that is secreted into the extracellular space and has been implicated in elastin and collagen degradation in diseases such as atherosclerosis. Elastin degradation plays an important role in vascular remodeling. However, the mechanism by which Cats regulate this process and its contribution to vein graft remodeling remain unclear.Methods and ResultsUsing a murine vein graft model, we examined the expression pattern of Cat family members. Expression of cathepsin genes was induced in vein grafts, with that of Cat S being the highest. Elevated Cat S expression was confirmed in both mouse and human vein grafts. To explore the role of Cat S, vein grafts were created between wild-type (WT) littermates and cathepsin S knockout (CatS KO) mice. Knockout of Cat S in the recipients (vein(CatS-KO)-artery(CatS-KO) or vein(WT)-artery(CatS-KO)) significantly inhibited neointima formation and reduced the accumulation of macrophages and proliferation of smooth muscle cells in vein grafts. Knockout of Cat S preserved the elastic fiber integrity of vein grafts and inhibited the migration of macrophages across the elastin fibers.
CONCLUSION: These results demonstrated that Cat S contributes to macrophage migration via degradation of elastic fiber integrity to facilitate neointima formation of vein grafts, which might provide a novel therapeutic target for preserving vein graft patency.
Authors:
Hong-Tao Shi; Ying Wang; Li-Xin Jia; Yan-Wen Qin; Yan Liu; Hui-Hua Li; Yong-Fen Qi; Jie Du
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-12-6
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Beijing An Zhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
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