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The effect of matrix metalloproteinase 2 and matrix metalloproteinase 2/9 deletion in experimental post-thrombotic vein wall remodeling  Kristopher B.

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Presentation on theme: "The effect of matrix metalloproteinase 2 and matrix metalloproteinase 2/9 deletion in experimental post-thrombotic vein wall remodeling  Kristopher B."— Presentation transcript:

1 The effect of matrix metalloproteinase 2 and matrix metalloproteinase 2/9 deletion in experimental post-thrombotic vein wall remodeling  Kristopher B. Deatrick, MD, Catherine E. Luke, LVT, Megan A. Elfline, BS, Vikram Sood, BS, Joseph Baldwin, BS, Gilbert R. Upchurch, MD, Farouc A. Jaffer, MD, PhD, Thomas W. Wakefield, MD, Peter K. Henke, MD  Journal of Vascular Surgery  Volume 58, Issue 5, Pages e2 (November 2013) DOI: /j.jvs Copyright © 2013 Society for Vascular Surgery Terms and Conditions

2 Fig 1 Thrombus size as measured by weight:length ratio showed larger venous thrombosis (VT) at day 8 in matrix metalloproteinase (MMP)2 -/- mice (A). Thrombus channels were fewer in MMP2 -/- mice compared with wild type (WT) (B). Photomicrographs in WT (C) show numerous channels in periphery of the thrombus. Fewer von Willebrand's factor (vWF) + channels noted in MMP2 -/- VT (D). At ×400, arrows mark channels. T, Thrombus; W, wall. White bar = 10 μm. Journal of Vascular Surgery  , e2DOI: ( /j.jvs ) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

3 Fig 2 A, Vein wall collagen content was less in matrix metalloproteinase (MMP)2 -/- compared with wild type (WT). Sirius red stained vein wall section of WT (B), contrasting with the thinner and less dense collagen (red) in the MMP2 -/- vein walls (C). Histologic images at ×100. Procollagen I was not altered in the MMP2 -/- vein wall compared with WT (D), while procollagen III was reduced at 8 days (E). Tropoelastin gene expression was reduced at 8 days in the MMP2 -/- compared with WT (F). T, Thrombus. *P < .05. Journal of Vascular Surgery  , e2DOI: ( /j.jvs ) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

4 Fig 3 Vein wall tumor necrosis factor-alpha (TNFα) in matrix metalloproteinase (MMP)2 -/- was less at 2 and 8 days (A), while interleukin (IL)-1β was reduced at 2 days (B). C, Vein wall active MMP9 activity was increased in MMP2 -/- mice at 8 days by zymography. D, Vein wall monocytes were increased at 8 days in MMP2 -/- mice compared with wild type (WT). E-G, Apoptosis as marked by terminal deoxynucleotidyl transferase end labeling (TUNEL) + green colocalized with 4′,6-diamidino-2-phenylindole blue staining nuclei showed less medial + cells at 8 days in the MMP2 -/- vein wall compared with WT. At ×400. T, Thrombus; W, wall; arrows mark + cells; *P < .05. White measurement bar = 10 μm. Journal of Vascular Surgery  , e2DOI: ( /j.jvs ) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

5 Fig 4 A, Thrombus size was increased at 8 days in matrix metalloproteinase (MMP)9 -/- + MMP2 inhibitor as well as MMP2/9 -/- double null mice. B, Collagen content was reduced in the MMP9 -/- + MMP2 inhibitor and the MMP2/9 -/- double null compared with wild type (WT). C, Monocytes were elevated in MMP9 -/- + MMP2 inhibition and MMP2/9 double null -/- mice. D-F, Representative photomicrographs of WT, MMP9 -/- + MMP2 inhibition, and MMP2/9 -/- mice. Histologic images at ×100. T, Thrombus; *P < .05 by analysis of variance with Dunnett multiple comparison test. #P < .05; ###P < .001 by analysis of variance with Bonferonni correction. Journal of Vascular Surgery  , e2DOI: ( /j.jvs ) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

6 Supplementary Fig 1 (online only)
Representative polarized photomicrographs of Sirius red stained nonthrombosed vein, and 2, 8, and 21 days thrombosed inferior vena cava (IVC) sections. Collagen is white. Note vein wall thickening over time after thrombosis. The arrows demarcate the vein wall. T, Thrombus. Journal of Vascular Surgery  , e2DOI: ( /j.jvs ) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

7 Supplementary Fig 2 (online only)
Photomicrographs of 8 days hematoxylin and eosin (H&E) stained thrombosed inferior vena cava (IVC) sections in wild type (WT) and in matrix metalloproteinase (MMP)2 -/- mice. Higher-power views show medial and intimal layers of the vein wall. Note no difference in intimal layers as denoted by the arrow. T, Thrombus. Journal of Vascular Surgery  , e2DOI: ( /j.jvs ) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

8 Supplementary Fig 3 (online only)
Representative panels of wild type (WT) C57 and C57 in matrix metalloproteinase (MMP)2 -/- at ×400. Arrows denote + Mac2 cells. Fewer are present in the WT vein wall. T, Thrombus; W, wall. Journal of Vascular Surgery  , e2DOI: ( /j.jvs ) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

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