Cathepsin S contributes to macrophage migration via degradation of elastic fibre integrity to facilitate vein graft neointimal hyperplasia

Hong Tao Shi, Ying Wang, Li Xin Jia, Yan Wen Qin, Yan Liu, Hui Hua Li, Yong Fen Qi, Jie Du

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

AimsCathepsin 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.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 Cat S knockout (Cat S KO) mice. Knockout of Cat S in the recipients (vein CatS-KO-arteryCatS-KO or veinWT-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.ConclusionThese 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.

Original languageEnglish (US)
Pages (from-to)454-463
Number of pages10
JournalCardiovascular research
Volume101
Issue number3
DOIs
StatePublished - Mar 1 2014

Keywords

  • Cathepsin S
  • Elastin
  • Hyperplasia
  • Neointima
  • Vein graft

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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