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

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.

TGF-β1 and Serpine 1 expression changes in traumatic deep vein thrombosis

“…Serpine 1 is primarily synthetized by liver cells, fibroblasts, myocardial cells, macrophages, fat cells, and vascular endothelial cells. In-depth research has found that platelets can also store and synthetize Serpine 1 (Deatrick et al, 2013). Platelet activation would therefore be predicted to release a large quantity of Serpine 1 molecules, which could facilitate thrombosis by inhibiting thrombus degradation.…”

Detection of targets and their mechanisms for early diagnosis of traumatic deep vein thrombosis

“…PAI-1 is a type of serine proteinase inhibitor, and it can be secreted by vascular endothelial cells, fibroblasts, and macrophages (Deatrick et al, 2013). PAI-1 can inhibit t-PA activation and reduce fiber dissolving characteristics locally, thus regulating the fibrinolytic system balance.…”

Plasminogen activator‐1 overexpression decreases experimental postthrombotic vein wall fibrosis by a non‐vitronectin‐dependent mechanism

“…From the current study, the mechanisms of PAI‐1 antifibrotic effect are likely two‐fold; first, significantly decreased MMP‐2 and ‐9 activity in the postthrombotic vein wall was found. Elevation of both MMPs is associated with postthrombotic vein wall fibrosis , and a reduction is consistent with attenuated fibrotic injury. Second, fewer macrophages (and consistently decreased MCP‐1) were found in the vein wall and thrombus of PAI‐1 Tg and Vn −/− mice.…”