Thrombogenesis with continuous blood flow in the inferior vena cava A novel mouse model

被引:56
作者
Diaz, Jose A. [1 ]
Hawley, Angela E.
Alvarado, Christine M. [2 ]
Berguer, Alexandra M.
Baker, Nichole K.
Wrobleski, Shirley K.
Wakefield, Thomas W.
Lucchesi, Benedict R. [3 ]
Myers, Daniel D., Jr. [2 ]
机构
[1] Univ Michigan, Conrad Jobst Vasc Res Labs, Dept Surg, Vasc Surg Sect, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Unit Lab Anim Med, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA
关键词
Endothelial dysfunction; thrombosis; electrolytic injury; inflammation; animal model; DEEP-VEIN THROMBOSIS; ANTIPHOSPHOLIPID ANTIBODIES; VENOUS THROMBOSIS; FACTOR-VIII; P-SELECTIN; MICE; INDUCTION; MONOCYTE; IGG;
D O I
10.1160/TH09-09-0672
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Several rodent models have been used to study deep venous thrombosis (DVT). However, a model that generates consistent venous thrombi in the presence of continuous blood flow, to evaluate therapeutic agents for DVT, is not available. Mice used in the present study were wild-type C57BL/6 (WT), plasminogen activator inhibitor-1 (PAI-1) knock out (KO) and Delta Cytoplasmic Tail (Delta CT). An electrolytic inferior vena cava (IVC) model (EIM) was used. A 25G stainless-steel needle, attached to a silver coated copper wire electrode (anode), was inserted into the exposed caudal IVC. Another electrode (cathode) was placed subcutaneously. A current of 250 mu Amps over 15 minutes was applied. Ultrasound imaging was used to demonstrate the presence of IVC blood flow. Analyses included measurement of plasma soluble P-selectin (sP-Sel), thrombus weight (TW), vein wall morphometrics, P-selectin and Von Willebrand factor (vWF) staining, transmission electron microoxaparin on TW was evaluated. A current of 250 mu Amps over 15 minutes consistently promoted thrombus formation in the IVC. Plasma sP-Sel was decreased in PAI-1 KO and increased in Delta CT vs. WT (WT/PAI-1: p=0.003, WT/Delta CT: p=0.0002). Endothelial activation was demonstrated by SEM, TEM, P-selectin and vWF immunohistochemistry and confirmed by inflammatory cell counts. Ultrasound imaging demonstrated thrombus formation in the presence of blood flow. Enoxaparin significantly reduced the thrombus size by 61% in this model. This El M closely mimics clinical venous disease and can be used to study endothelial cell activation, leukocyte migration, thrombogenesis and therapeutic applications in the presence of blood flow.
引用
收藏
页码:366 / 375
页数:10
相关论文
共 25 条
[1]   Glycoprotein Ibα and von Willebrand factor in primary platelet adhesion and thrombus formation:: Lessons from mutant mice [J].
Bergmeier, Wolfgang ;
Chauhan, Anil K. ;
Wagner, Denisa D. .
THROMBOSIS AND HAEMOSTASIS, 2008, 99 (02) :264-270
[2]   The role of the monocyte in the generation and dissolution of arterial and venous thrombi [J].
Burnand, KG ;
Gaffney, PJ ;
McGuinness, CL ;
Humphries, J ;
Quarmby, JW ;
Smith, A .
CARDIOVASCULAR SURGERY, 1998, 6 (02) :119-125
[3]   ADAMTS13: a new link between thrombosis and inflammation [J].
Chauhan, Anil K. ;
Kisucka, Janka ;
Brill, Alexander ;
Walsh, Meghan T. ;
Scheiflinger, Friedrich ;
Wagner, Denisa D. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (09) :2065-2074
[4]   von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins [J].
Chauhan, Anil K. ;
Kisucka, Janka ;
Lamb, Colin B. ;
Bergmeier, Wolfgang ;
Wagner, Denisa D. .
BLOOD, 2007, 109 (06) :2424-2429
[5]   A murine model of deep vein thrombosis - Characterization and validation in transgenic mice [J].
Cooley, BC ;
Szema, L ;
Chen, CY ;
Schwab, JP ;
Schmeling, G .
THROMBOSIS AND HAEMOSTASIS, 2005, 94 (03) :498-503
[6]  
Council N.R., 1996, GUIDE CARE USE LAB A, P1
[7]   Murine thrombosis models [J].
Day, SM ;
Reeve, JL ;
Myers, DD ;
Fay, WP .
THROMBOSIS AND HAEMOSTASIS, 2004, 92 (03) :486-494
[8]   Plasminogen activator inhibitor-1 and vitronectin promote vascular thrombosis in mice [J].
Eitzman, DT ;
Westrick, RJ ;
Nabel, EG ;
Ginsburg, D .
BLOOD, 2000, 95 (02) :577-580
[9]   INTIMAL ALTERATIONS IN RABBIT AORTAS DURING THE 1ST 6 MONTHS OF ALLOXAN-INDUCED DIABETES [J].
HADCOCK, S ;
RICHARDSON, M ;
WINOCOUR, PD ;
HATTON, MWC .
ARTERIOSCLEROSIS AND THROMBOSIS, 1991, 11 (03) :517-529
[10]   Deep vein thrombosis resolution is modulated by monocyte CXCR2-mediated activity in a mouse model [J].
Henke, PK ;
Varga, A ;
De, S ;
Deatrick, CB ;
Eliason, J ;
Arenberg, DA ;
Sukheepod, P ;
Thanaporn, P ;
Kunkel, SL ;
Upchurch, GR ;
Wakefield, TW .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2004, 24 (06) :1130-1137