Animal models of vulnerable plaque

Harry C. Lowe; Ik-Kyung Jang; Levon M. Khachigian

doi:10.1160/TH03-06-0374

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 90(05): 774-780
DOI: 10.1160/TH03-06-0374

Review Article

Schattauer GmbH

Animal models of vulnerable plaque

Clinical context and current status

Harry C. Lowe

¹Centre for Vascular Research, The University of New South Wales, Australia

²Cardiology Department, Concord Repatriation General Hospital, University of Sydney, Sydney, NSW, Australia

,

Ik-Kyung Jang

³Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

,

Levon M. Khachigian

¹Centre for Vascular Research, The University of New South Wales, Australia

› Author Affiliations

Abstract

Summary

There is increasing recognition of the importance of vulnerable plaque and acute plaque rupture leading to thrombosis, in the pathogenesis of acute coronary syndromes. This is fueling a number of developments, including novel imaging modalities and potential plaque stabilization therapies. However, to date, no animal model of vulnerable plaque or plaque rupture has been established. Recent developments, particularly using Apo E knockout mice, appear set to provide key breakthroughs. The present status of our understanding of plaque vulnerability is therefore discussed, with a discussion of these current advances in animal models.

Keywords

Animal models - atherosclerosis - ischaemic heart disease

Full Text

References

References
1 Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995; 92: 657-71.
2 Farb A. et al Sudden coronary death. Frequency of active coronary lesions, inactive coronary lesions, and myocardial infarction. Circulation 1995; 92: 1701-9.
3 Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995; 91: 2844-50.
4 Shah PK. Pathophysiology of coronary thrombosis: role of plaque rupture and plaque erosion. Prog Cardiovasc Dis 2002; 44: 357-68.
5 Shah PK. Mechanisms of plaque vulnerability and rupture. J Am Coll Cardiol 2003; 41 (04) (Suppl S) 15-22.
6 Davies MJ. The pathophysiology of acute coronary syndromes. Heart 2000; 83: 361-6.
7 Rekhter MD. How to evaluate plaque vulnerablity in animal models of atherosclerosis ?. Cardiovasc Res 2002; 54: 36-41.
8 Cullen P, Buetta R, Bellosta S. et al Rupture of the atherosclerotic plaque: does a good animal model exist?. Arterioscler Thromb Vasc Biol 2003; 23: 535-42.
9 Muller JE, Tofler G. Triggering and hourly variation of onset of arterial thrombosis. Ann Epidemiol 1992; 4: 393-405.
10 Virmani R, Burke AP, Farb A. et al Pathology of the unstable plaque. Prog Cardiovasc Dis 2002; 44: 349-56.
11 Burke AP, Farb A, Malcom GT. et al Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997; 336: 1276-82.
12 Virmani R, Kolodgie F, Burke AP. et al Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2000; 20: 1262-75.
13 Farb A, Burke A, Tang AL. Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation 1996; 93: 1354-63.
14 Kereiakes DJ. The Emperor’s clothes: in search of the vulnerable plaque. Circulation 2003; 107: 2076-7.
15 Felton CV. et al Relation of plaque lipid composition and morphology to the stability of human aortic plaques. Arteriosclerosis, Thromb Vasc Biol 1997; 17: 1337-45.
16 Takano M, Mizuno K, Okamatsu K. et al Mechanical and structural characteristics of vulnerable plaques: analysis by coronary angioscopy and intravascular ultrasound. J Am Coll Cardiol 2001; 38: 99-104.
17 Cheng GC, Loree H, Kamm RD. et al Distribution of circumferential stress in ruptured and stable atherosclerotic lesions. A structural analysis with histopathological correlation. Circulation 1993; 87: 1179-87.
18 Toschi V, Gallo R, Lettino M. et al Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. Circulation 1997; 95: 594-9.
19 Fernandez-Ortiz A, Badimon J, 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: 1562-9.
20 Laine P, Kaartinen M, Penttila A, Pet al. Association between myocardial infarction and the mast cells in the adventitia of the infarct-related coronary artery. Circulation 1999; 99: 361-9.
21 Libby P. Changing concepts of atherogenesis. J Intern Med 2000; 247: 349-58.
22 Burleigh MC, Briggs A, Lendon CL. et al Collagen types I and III, collagen content, GAGs and mechanical strength of human atherosclerotic plaque caps: span-wise variations. Atherosclerosis 1992; 96: 71-81.
23 Libby P, Aikawa M. Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat Med 2002; 8: 1257-62.
24 Geng YJ, Libby P. Progression of atheroma: a struggle between death and procreation. Arterioscler, Thromb Vasc Biol 2002; 22: 1370-80.
25 Thornberry NA, Lazebnik Y. Caspases: enemies within. Science 1998; 281: 1312-6.
26 Evan G, Littlewood T. A matter of life and death. Science 1998; 281: 1317-22.
27 Young JL, Libby P, Schonbeck U. Cytokines in the pathogenesis of atherosclerosis. Thromb Haemost 2002; 88: 554-67.
28 Walsh K, Smith R, Kim HS. Vascular cell apoptosis in remodeling, restenosis, and plaque rupture. Circ Res 2000; 87: 184-8.
29 Falk E. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi. Br Heart J 1983; 50: 127-34.
30 Ambrose JA, Winters S, Arora RR. et al Coronary angiographic morphology in myocardial infarction: a link between the pathogenesis of unstable angina and myocardial infarction. J Am Coll Cardiol 1985; 6: 1233-8.
31 Ambrose JA, Winters S, Stern A. et al. Angio-graphic morphology and the pathogenesis of unstable angina pectoris. J Am Coll Cardiol. 1985; 5: 609-16.
32 Ge J. et al Screening of ruptured plaques in patients with coronary artery disease by intravascular ultrasound. Heart 1999; 81: 621-7.
33 Sherman CT, Litvack F, Grundfest W. et al Coronary angioscopy in patients with unstable angina pectoris. N Engl J Med 1986; 315: 913-9.
34 Newby AC, Libby P, van der Wal AC. Plaque instability—the real challenge for atherosclerosis research in the next decade?. Cardiovasc Res 1999; 41: 321-2.
35 Blake GJ, Ridker P. Inflammatory bio-markers and cardiovascular risk prediction. J Intern Med 2002; 252: 283-94.
36 Buffon A, Biasucci LM, Liuzzo G. et al. Widespread coronary inflammation in unstable angina. N Engl J Med 2002; 347: 5-12.
37 Maseri A, Fuster V. Is there a vulnerable plaque?. Circulation 2003; 107: 2068-71.
38 Casscells W, Naghavi M, Willerson JT. Vulnerable atherosclerotic plaque: a multifo-cal disease. Circulation 2003; 107: 2072-5.
39 Mac Neill BD, Lowe HC, Takano M. et al Intravascular modalities for detection of vulnerable plaque: Current status. Arterioscler Thromb Vasc Biol 2003; 23: 1333-42.
40 Nissen SE. Pathobiology, not angiography, should guide managementin acute coronary syndrome/non-ST-segment elevation myocardial infarction. The non-interventionist’s perspective. J Am Coll Cardiol 2003; 41 (04) (suppl S) S103-12.
41 Stefanadis C. et al Thermal heterogeneity within human atherosclerotic coronary arteries detected in vivo: A new method of detection by application of a special thermography catheter. Circulation 1999; 99: 1965-71.
42 Madjid M, Naghevi M, Malik BA. et al Thermal detection of vulnerable plaque. Am J Cardiol 2002; 90: 36L-39L.
43 Moreno PR, Lodder RA, Purushothaman KR. et al Detection of lipid pool, thin fibrous cap, and inflammatory cells in human aortic atherosclerotic plaques by near-infrared spectroscopy. Circulation 2002; 105: 923-7.
44 Tearney GJ, Yabushita H, Houser SL. et al Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography. Circulation 2002; 107: 113-9.
45 Weissleder R, Ntziachristos V. Shedding light onto live molecular targets. Nat Med 2003; 9: 123-8.
46 Chen J, Tung CH, Mahmood U. et al In vivo imaging of proteolytic activity in atherosclerosis. Circulation 2002; 105: 2766-71.
47 Bremer C, Tung CH, Weissleder R. Molecular imaging of MMP expression and therapeutic MMP inhibition. Acad Radiol 2002; 9 (02) S314-5.
48 Popma JJ, Kuntz RE, Baim DS. A decade of improvement in the clinical outcomes of percutaneous coronary intervention for multivessel disease. Circulation 2002; 106: 1592-4.
49 Bustos C. et al HMG-CoA reductase inhibition by atorvastatin reduces neointimal inflammation in a rabbit model of atherosclerosis. J Am Coll Cardiol 1998; 32: 2057-64.
50 Aikawa M. et al. An HMG-CoA reductase inhibitor, cerivastatin, suppresses growth of macrophages expressing matrix metalloproteinases and tissue factor in vivo and in vitro. Circulation 2001; 103: 276-83.
51 Badimon L. Atherosclerosis and thrombosis: lessons from animal models. Thromb Haemost 2001; 86: 356-65.
52 Fuster V, Ip JH, Badimon L. et al Importance of experimental models for the development of clinical trials on thromboatherosclerosis. Circulation 1991; 83: IV15-IV25.
53 Rekhter M. How to evaluate plaque vulnerablity in animal models of atherosclerosis?. Car-diovasc Res 2002; 54: 36-41.
54 Shiomi M, Ito T, Hirouchi Y. et al Fibromuscular cap composition is important for the stability of established atherosclerotic plaques in mature WHHL rabbits treated with statins. Atherosclerosis 2001; 157: 75-84.
55 Moons AHM, Levi M, Peters RJG. Tissue factor and coronary artery disease. Cardiovasc Res 2002; 53: 313-25.
56 Taubman MB, Fallon JH, Schecter AD. et al Tissue factor in the pathogenesis of atherosclerosis. Thromb Haemost 1997; 78: 200-4.
57 Bennett MR. Apoptosis of vascular smooth muscle cells in vascular remodelling and atherosclerotic plaque rupture. Cardiovasc Res 1999; 41: 361-8.
58 Galis ZS, Sukhova GK, Lark MW. et al Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 1994; 94: 2493-503.
59 Sukhova G, Shi GP, Simon D I. et al Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. J Clin Invest 1998; 102: 576-83.
60 Constantinides P, Chakravarti RH. Rabbit arterial thrombosis production by sysytemic procedures. Arch Pathol 1961; 72: 197-208.
61 Abela GS, Picon PD, Friedl SE. et al Triggering of plaque disruption and arterial thrombosis in an atherosclerotic rabbit model. Circulation 1995; 91: 776-84.
62 Nakamura M, Abe S, Kinukawa N. Aortic medial necrosis with or without thrombosis in rabbits treated with Russell’s viper venom and angiotensin II. Atherosclerosis 1997; 128: 149-56.
63 Rekhter MD, Hicks GW, Brammer DW. et al Animal model that mimics atherosclerotic plaque rupture. CIrculation Res 1998; 83: 705-13.
64 Keelan PC, Bayes-Genis A, Kantor B. et al A novel porcine model for in vivo detection of vulnerable plaque: deposition and localization of lipid-rich lesions in the coronary artery wall. Circulation 2001; 98: II-67.
65 Prescott MF, McBride CH, Hasler-Rapacz J. et al Development of complex atherosclerotic lesions in pigs with inherited hyper-LDL cholesterolemia bearing mutant alleles for apolipoprotein B. Am J Pathol 1991; 139: 139-47.
66 Krantz DS, Kop WJ, Santiago HT. et al. Mental stress as a trigger of myocardial ischemia and infarction. Cardiology Clinics 1996; 14: 271-87.
67 Caligiuri G, Levy B, Pernow J. et al Myocardial infarction mediated by endothelin receptor signaling in hypercholesterolemic mice. Proc Natl Acad Sci USA 1999; 96: 6920-4.
68 Eitzman DT, Westrick RJ, Xu Z. et al Plasminogen activator inhibitor-1 deficiency protects against atherosclerosis progression in the mouse carotid artery. Arterioscler Thromb Vasc Biol 2000; 20: 846-52.
69 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: 2064-70.
70 Herrera VL, Makrides SL, Xie HX. et al Spontaneous combined hyperlipidemia, coronary heart disease and decreased survival in Dahl salt-sensitive hypertensive rats transgenic for human cholesteryl ester transfer protein. Nat Med 1999; 5: 1383-9.
71 Reddick RL, Zhang SH, Maeda N. Atherosclerosis in mice lacking apo E. Evaluation of lesional development and progression. Arterioscler Thromb 1994; 14: 141-7.
72 Seo HS. et al Peripheral vascular stenosis in apolipoprotein E-deficient mice. Potential roles of lipid deposition, medial atrophy, and adventitial inflammation. Arteriosclerosis, Thromb Vasc Biol 1997; 17: 3593-601.
73 Rosenfeld ME. et al Advanced atherosclero-tic lesions in the innominate artery of the ApoE knockout mouse. Arterioscler Thromb Vasc Biol 2000; 20: 2587-92.
74 Getz GS. Mouse model of unstable atherosclerotic plaque ?. Arterioscler Thromb Vascr Biol 2000; 20: 2503-5.
75 Williams H, Johnson JL, Carson KGS. et al Characteristics of intact and ruptured atherosclerotic plaques in brachiocephalic arteries of apolipotprotein E knockout mice. Arterioscler Thromb Vasc Biol 2002; 22: 788-92.
76 Bennett MR. Breaking the Plaque: evidence for plaque rupture in animal models of atherosclerosis. Arterioscler Thromb Vasc Biol 2002; 22: 713-4.
77 Libby P. Inflammation in atherosclerosis. Nature 2002; 420: 868-74.
78 van der Wal AC, Becker AE, van der Loos CM. et al Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 1994; 89: 36-44.
79 Tenaglia AN, Peters KG, Sketch Jr MH. et al Neovascularization in atherectomy specimens from patients with unstable angina: implications for pathogenesis of unstable angina. Am Heart J 1998; 135: 10-4.