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

被引:48
作者
Deatrick, Kristopher B. [1 ]
Obi, Andrea [1 ]
Luke, Catherine E. [1 ]
Elfline, Megan A. [1 ]
Sood, Vikram [1 ]
Upchurch, Gilbert R., Jr. [1 ]
Jaffer, Farouc [2 ,3 ]
Wakefield, Thomas W. [1 ]
Henke, Peter K. [1 ]
机构
[1] Univ Michigan, Conrad Jobst Vasc Res Lab, Vasc Surg Sect, Sch Med,Dept Surg, Boston, MA USA
[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA
[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA
关键词
Venous thrombosis; Inflammation; Matrix metalloproteinases; Monocytes; VENOUS THROMBOSIS RESOLUTION; MOLECULAR-WEIGHT HEPARIN; MUSCLE-CELL MIGRATION; MATRIX METALLOPROTEINASES; MOUSE MODEL; TISSUE INHIBITORS; INFLAMMATION; COLLAGEN; INJURY; POLARIZATION;
D O I
10.1016/j.thromres.2013.06.027
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
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. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:360 / 366
页数:7
相关论文
共 38 条
[1]
Regulation of endothelial barrier function by TGF-β type I receptor ALK5: Potential role of contractile mechanisms and heat shock protein 90 [J].
Antonov, Alexander S. ;
Antonova, Galina N. ;
Fujii, Makiko ;
Ten Dijke, Peter ;
Handa, Vaishali ;
Catravas, John D. ;
Verin, Alexander D. .
JOURNAL OF CELLULAR PHYSIOLOGY, 2012, 227 (02) :759-771
[2]
Baldwin JD, 2012, ECOL APPL, V22, P1
[3]
Mechanisms of disease:: Chronic venous disease [J].
Bergan, John J. ;
Schmid-Schoenbein, Geert W. ;
Smith, Philip D. Coleridge ;
Nicolaides, Andrew N. ;
Boisseau, Michel R. ;
Eklof, Bo .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (05) :488-498
[4]
Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury [J].
Cho, A ;
Reidy, MA .
CIRCULATION RESEARCH, 2002, 91 (09) :845-851
[5]
Collagen in the scarless fetal skin wound: Detection with Picrosirius-polarization [J].
Cuttle, L ;
Nataatmadja, M ;
Fraser, JF ;
Kempf, M ;
Kimble, RM ;
Hayes, MT .
WOUND REPAIR AND REGENERATION, 2005, 13 (02) :198-204
[6]
Differential transcriptional activation of matrix metalloproteinase-2 and membrane type-1 matrix metalloproteinase by experimental deep venous thrombosis and thrombin [J].
Dahi, S ;
Lee, JG ;
Lovett, DH ;
Sarkar, R .
JOURNAL OF VASCULAR SURGERY, 2005, 42 (03) :539-545
[7]
Vein wall remodeling after deep vein thrombosis involves matrix metalloproteinases and late fibrosis in a mouse model [J].
Deatrick, KB ;
Eliason, JL ;
Lynch, EM ;
Moore, AJ ;
Dewyer, NA ;
Varma, MR ;
Pearce, CG ;
Upchurch, GR ;
Wakefield, TW ;
Henke, PK .
JOURNAL OF VASCULAR SURGERY, 2005, 42 (01) :140-148
[8]
Postthrombotic vein wall remodeling: Preliminary observations [J].
Deatrick, Kristopher B. ;
Elfline, Megan ;
Baker, Nichole ;
Luke, Catherine E. ;
Blackburn, Susan ;
Stabler, Catherine ;
Wakefield, Thomas W. ;
Henke, Peter K. .
JOURNAL OF VASCULAR SURGERY, 2011, 53 (01) :139-146
[9]
Plasmin inhibition increases MMP-9 activity and decreases vein wall stiffness during venous thrombosis resolution [J].
Dewyer, Nicholas A. ;
Sood, Vikram ;
Lynch, Erin M. ;
Luke, Catherine E. ;
Upchurch, Gilbert R., Jr. ;
Wakefield, Thomas W. ;
Kunkel, Steven ;
Henke, Peter K. .
JOURNAL OF SURGICAL RESEARCH, 2007, 142 (02) :357-363
[10]
Matrix metalloproteinases in vascular remodeling and atherogenesis - The good, the bad, and the ugly [J].
Galis, ZS ;
Khatri, JJ .
CIRCULATION RESEARCH, 2002, 90 (03) :251-262