Matrix metalloproteinase-9 deletion is associated with decreased mid-term vein wall fibrosis in experimental stasis DVT

• Published in: Thrombosis research 2013-09, Vol.132 (3), p.360-366
• Main Authors: Deatrick, Kristopher B, Obi, Andrea, Luke, Catherine E, Elfline, Megan A, Sood, Vikram, Upchurch, Gilbert R, Jaffer, Farouc, Wakefield, Thomas W, Henke, Peter K
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; Fibrosis; Gene Expression; Hematology, Oncology and Palliative Medicine; Inflammation; Leukocytes, Mononuclear - enzymology; Leukocytes, Mononuclear - pathology; Male; Matrix Metalloproteinase 9 - deficiency; Matrix Metalloproteinase 9 - metabolism; Matrix metalloproteinases; Mice; Mice, Knockout; Monocytes; Veins - enzymology; Veins - pathology; Venous thrombosis; Venous Thrombosis - enzymology; Venous Thrombosis - genetics; Venous Thrombosis - pathology
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2013.06.027

Abstract Introduction 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 21 days. 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.