Comparison of two murine models of thrombosis induced by atherosclerotic plaque injury

Béatrice Hechler; Christian Gachet

doi:10.1160/THS10-11-0730

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2011; 105(S 06): S3-S12
DOI: 10.1160/THS10-11-0730

Thrombosis and Haemostasis Supplement

Schattauer GmbH

Comparison of two murine models of thrombosis induced by atherosclerotic plaque injury

Authors

Béatrice Hechler

¹UMR_S949 INSERM, Université de Strasbourg, Etablissement Français du Sang-Alsace, Strasbourg, France
Christian Gachet

¹UMR_S949 INSERM, Université de Strasbourg, Etablissement Français du Sang-Alsace, Strasbourg, France

Abstract

Summary

Arterial thrombosis occurs at sites of erosion or rupture of atherosclerotic vascular lesions. To better study the pathophysiology of this complex phenomenon, there is a need for animal models of localised thrombosis at sites of atherosclerotic lesions with closer resemblance to the human pathology as compared to commonly used thrombosis models in healthy vessels. In the present study, we describe and compare a new model of thrombosis induced by atherosclerotic plaque rupture in the carotid artery from ApoE^-/- mice using a suture needle to a milder model of ultrasound-induced plaque injury. Needle injury induces atherosclerotic plaque rupture with exposure of plaque material and formation of a thrombus that is larger, nearly occlusive and more stable as compared to that formed by application of ultrasounds. These two models have common features such as the concomitant involvement of platelet activation, thrombin generation and fibrin formation, which translates into sensitivity toward both antiplatelet drugs and anticoagulants. On the other hand, they display differences with respect to the role of the platelet collagen receptor GPVI, the plaque rupture model being less sensitive to its inhibition as compared to the ultrasound-induced injury, which may be related to the amount of thrombin generated. These models represent an improvement as compared to models in healthy vessels and may help identify specific plaque triggers of thrombosis. They should therefore be useful to evaluate new antithrombotic targets.

Keywords

Animal models - antiplatelet agents - atherosclerosis - arterial thrombosis - atherothrombosis

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Referenzen

References
1 Day SM, Reeve JL, Myers DD. et al. Murine thrombosis models. Thromb Haemost 2004; 92: 486-494.
2 Denis C, Methia N, Frenette PS. et al. A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis. Proc Natl Acad Sci USA 1998; 95: 9524-9529.
3 Kurz KD, Main BW, Sandusky GE. Rat model of arterial thrombosis induced by ferric chloride. Thromb Res 1990; 60: 269-280.
4 Matsuno H, Uematsu T, Nagashima S. et al. Photochemically induced thrombosis model in rat femoral artery and evaluation of effects of heparin and tissue-type plasminogen activator with use of this model. J Pharmacol Methods 1991; 25: 303-317.
5 Westrick RJ, Winn ME, Eitzman DT. Murine models of vascular thrombosis (Eitzman series). Arterioscler Thromb Vasc Biol 2007; 27: 2079-2093.
6 Falati S, Gross P, Merrill-Skoloff G. et al. Real-time in vivo imaging of platelets, tissue factor and fibrin during arterial thrombus formation in the mouse. Nat Med 2002; 8: 1175-1181.
7 Furie B, Furie BC. Mechanisms of thrombus formation. N Engl J Med 2008; 359: 938-949.
8 Nonne C, Lenain N, Hechler B. et al. Importance of platelet phospholipase Cgamma2 signaling in arterial thrombosis as a function of lesion severity. Arterioscler Thromb Vasc Biol 2005; 25: 1293-1298.
9 Celi A, Merrill-Skoloff G, Gross P. et al. Thrombus formation: direct real-time observation and digital analysis of thrombus assembly in a living mouse by confocal and widefield intravital microscopy. J Thromb Haemost 2003; 1: 60-68.
10 Hechler B, Nonne C, Eckly A. et al. Arterial thrombosis: relevance of a model with two levels of severity assessed by histologic, ultrastructural and functional characterization. J Thromb Haemost 2010; 8: 173-184.
11 Rosen ED, Raymond S, Zollman A. et al. Laser-induced noninvasive vascular injury models in mice generate platelet- and coagulation-dependent thrombi. Am J Pathol 2001; 158: 1613-1622.
12 Nieswandt B, Aktas B, Moers A. et al. Platelets in atherothrombosis: lessons from mouse models. J Thromb Haemost 2005; 3: 1725-1736.
13 Sachs UJ, Nieswandt B. In vivo thrombus formation in murine models. Circ Res 2007; 100: 979-991.
14 Barnes MJ, Farndale RW. Collagens and atherosclerosis. Exp Gerontol 1999; 34: 513-525.
15 Fernandez-Ortiz A, Badimon JJ, Falk E. et al. Characterization of the relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture. J Am Coll Cardiol 1994; 23: 1562-1569.
16 Katsuda S, Kaji T. Atherosclerosis and extracellular matrix. J Atheroscler Thromb 2003; 10: 267-274.
17 Siess W, Zangl KJ, Essler M. et al. Lysophosphatidic acid mediates the rapid activation of platelets and endothelial cells by mildly oxidized low density lipoprotein and accumulates in human atherosclerotic lesions. Proc Natl Acad Sci USA 1999; 96: 6931-6936.
18 van Zanten GH, de Graaf S, Slootweg PJ. et al. Increased platelet deposition on atherosclerotic coronary arteries. J Clin Invest 1994; 93: 615-632.
19 Ruggeri ZM. Platelets in atherothrombosis. Nat Med 2002; 8: 1227-1234.
20 Jawien J, Nastalek P, Korbut R. Mouse models of experimental atherosclerosis. J Physiol Pharmacol 2004; 55: 503-517.
21 Ni M, Chen WQ, Zhang Y. Animal models and potential mechanisms of plaque destabilisation and disruption. Heart 2009; 95: 1393-1398.
22 Reddick RL, Zhang SH, Maeda N. Aortic atherosclerotic plaque injury in apolipoprotein E deficient mice. Atherosclerosis 1998; 140: 297-305.
23 Kuijpers MJ, Gilio K, Reitsma S. et al. Complementary roles of platelets and coagulation in thrombus formation on plaques acutely ruptured by targeted ultrasound treatment: a novel intravital model. J Thromb Haemost 2009; 7: 152-161.
24 Gachet C, Cattaneo M, Ohlmann P. et al. Purinoceptors on blood platelets: further pharmacological and clinical evidence to suggest the presence of two ADP receptors. Br J Haematol 1995; 91: 434-444.
25 Nieswandt B, Schulte V, Bergmeier W. et al. Long-term antithrombotic protection by in vivo depletion of platelet glycoprotein VI in mice. J Exp Med 2001; 193: 459-469.
26 Carstairs KC. The identification of platelets and platelet antigens in histological sections. J Pathol Bacteriol 1965; 90: 225-231.
27 Perrault C, Mangin P, Santer M. et al. Role of the intracellular domains of GPIb in controlling the adhesive properties of the platelet GPIb/V/IX complex. Blood 2003; 101: 3477-3484.
28 Hagedorn I, Vogtle T, Nieswandt B. Arterial thrombus formation. Novel mechanisms and targets Novel mechanisms and targets. Hamostaseologie 2010; 30: 127-135.
29 Dubois C, Panicot-Dubois L, Merrill-Skoloff G. et al. Glycoprotein VI-dependent and -independent pathways of thrombus formation in vivo. Blood 2006; 107: 3902-3906.
30 Konstantinides S, Ware J, Marchese P. et al. Distinct antithrombotic consequences of platelet glycoprotein Ibalpha and VI deficiency in a mouse model of arterial thrombosis. J Thromb Haemost 2006; 4: 2014-2021.
31 Mangin P, Yap CL, Nonne C. et al. Thrombin overcomes the thrombosis defect associated with platelet GPVI/FcRgamma deficiency. Blood 2006; 107: 4346-4353.
32 Massberg S, Gawaz M, Gruner S. et al. A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo. J Exp Med 2003; 197: 41-49.
33 Eckly A, Hechler B, Freund M. et al. Mechanisms underlying FeCl3-induced arterial thrombosis. J Thromb Haemost. 2011 doi:10.1111/j.1538-7836.2011.04218.x.
34 Rabie T, Varga-Szabo D, Bender M. et al. Diverging signaling events control the pathway of GPVI down-regulation in vivo. Blood 2007; 110: 529-535.
35 Eitzman DT, Westrick RJ, Xu Z. et al. Plasminogen activator inhibitor-1 deficiency protects against atherosclerosis progression in the mouse carotid artery. Blood 2000; 96: 4212-4215.
36 Eitzman DT, Westrick RJ, Xu Z. et al. Hyperlipidemia promotes thrombosis after injury to atherosclerotic vessels in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2000; 20: 1831-1834.
37 Westrick RJ, Bodary PF, Xu Z. et al. Deficiency of tissue factor pathway inhibitor promotes atherosclerosis and thrombosis in mice. Circulation 2001; 103: 3044-3046.
38 Toschi V, Gallo R, Lettino M. et al. Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. Circulation 1997; 95: 594-599.
39 Reininger AJ, Bernlochner I, Penz SM. et al. A 2-step mechanism of arterial thrombus formation induced by human atherosclerotic plaques. J Am Coll Cardiol 2010; 55: 1147-1158.
40 Libby P, Okamoto Y, Rocha VZ. et al. Inflammation in atherosclerosis: transition from theory to practice. Circ J 2010; 74: 213-220.
41 Hechler B, Lenain N, Marchese P. et al. A role of the fast ATP-gated P2X1 cation channel in thrombosis of small arteries in vivo. J Exp Med 2003; 198: 661-667.
42 Podrez EA, Byzova TV, Febbraio M. et al. Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype. Nat Med 2007; 13: 1086-1095.
43 Schaff M, Receveur N, Bourdon C. et al. Novel function of tenascin-C, a matrix protein relevant to atherosclerosis, in platelet recruitment and activation under flow. Arterioscler Thromb Vasc Biol 2011; 31: 117-124.
44 Eijgelaar WJ, Heeneman S, Daemen MJ. The vulnerable patient: refocusing on the plaque?. Thromb Haemost 2009; 102: 231-239.
45 Libby P. Molecular and cellular mechanisms of the thrombotic complications of atherosclerosis. J Lipid Res 2009; 50 Suppl S352-357.
46 Thim T, Hagensen MK, Bentzon JF. et al. From vulnerable plaque to atherothrombosis. J Int Med 2008; 263: 506-516.
47 Calara F, Silvestre M, Casanada F. et al. Spontaneous plaque rupture and secondary thrombosis in apolipoprotein E-deficient and LDL receptor-deficient mice. J Pathol 2001; 195: 257-263.
48 Jackson CL. Defining and defending murine models of plaque rupture. Arterioscler Thromb Vasc Biol 2007; 27: 973-977.
49 Johnson JL, Jackson CL. Atherosclerotic plaque rupture in the apolipoprotein E knockout mouse. Atherosclerosis 2001; 154: 399-406.
50 Schwartz SM, Galis ZS, Rosenfeld ME. et al. Plaque rupture in humans and mice. Arterioscler Thromb Vasc Biol 2007; 27: 705-713.
51 de Nooijer R, von der Thusen JH, Verkleij CJ. et al. Overexpression of IL-18 decreases intimal collagen content and promotes a vulnerable plaque phenotype in apolipoprotein-E-deficient mice. Arterioscler Thromb Vasc Biol 2004; 24: 2313-2319.
52 Gough PJ, Gomez IG, Wille PT. et al. Macrophage expression of active MMP-9 induces acute plaque disruption in apoE-deficient mice. J Clin Invest 2006; 116: 59-69.
53 Zadelaar AS, von der Thusen JH, Boesten LS. et al. Increased vulnerability of pre-existing atherosclerosis in ApoE-deficient mice following adenovirus-mediated Fas ligand gene transfer. Atherosclerosis 2005; 183: 244-250.
54 von der Thusen JH, van Vlijmen BJ, Hoeben RC. et al. Induction of atherosclerotic plaque rupture in apolipoprotein E-/- mice after adenovirus-mediated transfer of p53. Circulation 2002; 105: 2064-2070.