title: Matrix metalloproteinase-9 deletion is associated with decreased mid-term vein wall fibrosis in experimental stasis DVT.
abstract: BACKGROUND
  Post thrombotic syndrome therapy is primarily palliative, and the associated vein wall inflammatory mechanisms are unclear. Vein wall fibrotic injury following deep venous thrombosis (VT) is associated with elevated matrix metalloproteinases (MMPs). Whether and by what mechanism MMP9 directly contributes to vein wall remodeling after VT is unknown.
  
  
  METHODS
  WT and MMP9 -/- mice underwent stasis VT by ligation of the inferior vena cava (IVC) and tissue was harvested at 2, 8, and 21days. Assessment of thrombus size, and gene, protein and structural vein wall determinations were done.
  
  
  RESULTS
  VT resolution was increased in MMP9-/- mice as compared with controls at 21d only. The primary phenotypic fibrotic vein wall differences occurred at 8d post VT, with significantly less vein wall collagen content as assessed by Picosirius red staining in MMP9 -/- mice as compared with WT. Increased monocytic vein wall influx with less IL-1b and TGFb was found in MMP9 -/- vein walls as compared with WT. Corresponding levels of PAI-1 were increased in MMP9 -/- compared with WT, and no difference in FSP-1+cells as compared with controls.
  
  
  CONCLUSIONS
  In stasis VT, MMP9 modulates midterm vein wall collagen content, with an altered local inflammatory and profibrotic environment, likely directed by monocytes. Thus, MMP9 plays a role in both vein wall responses as well as late thrombus resolution.
authors: Conrad Jobst Vascular Research Laboratory, Section of Vascular Surgery, Department of Surgery, University of Michigan Medical School, Boston MA, United States.
authors: Kristopher B
authors: KB
authors: Deatrick
authors: Andrea
authors: A
authors: Obi
authors: Catherine E
authors: CE
authors: Luke
authors: Megan A
authors: MA
authors: Elfline
authors: Vikram
authors: V
authors: Sood
authors: Gilbert R
authors: GR
authors: Upchurch
authors: Farouc
authors: F
authors: Jaffer
authors: Thomas W
authors: TW
authors: Wakefield
authors: Peter K
authors: PK
authors: Henke
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis; D015870:Gene Expression; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D014680:Veins / Q000201:enzymology / Q000473:pathology*; D020246:Venous Thrombosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*
chemical_list: D020780:Matrix Metalloproteinase 9
keywords: Inflammation; Matrix metalloproteinases; Monocytes; Venous thrombosis
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