title: Cathepsin S contributes to macrophage migration via degradation of elastic fibre integrity to facilitate vein graft neointimal hyperplasia.
abstract: OBJECTIVE
  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 remodelling. However, the mechanism by which Cat regulates this process and its contribution to vein graft remodelling remains unclear.
  
  
  RESULTS
  Using 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 Cat S knockout (Cat S 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 fibre integrity of vein grafts and inhibited the migration of macrophages across the elastin fibres.
  
  
  CONCLUSIONS
  These results demonstrated that Cat S contributes to macrophage migration via degradation of elastic fibre integrity to facilitate neointima formation of vein grafts, which might provide a novel therapeutic target for preserving vein graft patency.
authors: 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.
authors: Hong-Tao
authors: HT
authors: Shi
authors: Ying
authors: Y
authors: Wang
authors: Li-Xin
authors: LX
authors: Jia
authors: Yan-Wen
authors: YW
authors: Qin
authors: Yan
authors: Y
authors: Liu
authors: Hui-Hua
authors: HH
authors: Li
authors: Yong-Fen
authors: YF
authors: Qi
authors: Jie
authors: J
authors: Du
mesh_terms: D000818:Animals; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000473:pathology*; D006965:Hyperplasia / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058426:Neointima / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D015398:Signal Transduction / Q000502:physiology; D014680:Veins / Q000637:transplantation
chemical_list: D002403:Cathepsins; C028217:cathepsin S
keywords: Cathepsin S; Elastin; Hyperplasia; Neointima; Vein graft