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Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism

An Erratum to this article was published on 28 June 2016


Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis—often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Ruffer MA. On arterial lesions found in Egyptian mummies (1580 B.C.–525 A.D.). J Pathol Bacteriol. 1911;15:453.

    Article  Google Scholar 

  2. 2.

    Virchow R. Cellular pathology as based upon physiological and pathological histology (translated by Frank Chance from the 2nd German Edition) London: John Churchill, 1860:p.360.

  3. 3.

    Rokitanski C. A manual of pathological anatomy (translated by William Swaine from German). Vol. 1. London: Sydenham Society, 1854:p.97.

  4. 4.

    Stehbens WE. Anitschkow and the cholesterol over-fed rabbit. Cardiovasc Pathol. 1999;8:177–8.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Finking G, Hanke H. Nikolaj Nikolajewitsch Anitschkow (1885–1964) established the cholesterol-fed rabbit as a model for atherosclerosis research. Atherosclerosis. 1997;135:1–7.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Constantinides P. Plaque fissures in human coronary thrombosis. J Atheroscler Res. 1996;80:19–44.

    Google Scholar 

  7. 7.

    Davies MJ, Thomas AC. Plaque fissuring: the cause of acute myocardial infarction causing sudden ischaemic death, and crescendo angina. Br Heart J. 1985;53:363–73.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Constantinides P, Chakravarti RN. Rabbit arterial thrombosis production by systemic procedures. Arch Pathol. 1961;71:197–208.

    Google Scholar 

  9. 9.

    Ross R, Glomset JA. The pathogenesis of atherosclerosis (First of two parts). N Engl J Med. 1976;295:369–77.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Ross R, Glomset JA. The pathogenesis of atherosclerosis (second of two parts). N Engl J Med. 1976;295:420–5.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Steinberg D, Witztum JL. Oxidized low-density lipoprotein and atherosclerosis. Arterioscler Thromb Vasc Biol. 2010;30:2311–6.

    CAS  Article  PubMed  Google Scholar 

  12. 12.•

    Düwell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind F, et al. NLRP3 Inflamasomes are required for atherogenesis and activated by cholesterol crystals that form early in disease. Nature. 2010;464:1357–62. This report demonstrates for the first time the role of cholesterol crystals in triggering the inflammation cascade leading to IL-1β production.

    Article  Google Scholar 

  13. 13.

    Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473:317–25.

    CAS  Article  PubMed  Google Scholar 

  14. 14.••

    Janoudi A, Shamoun FE, Kalavakunta JK, Abela GS. Cholesterol crystal induced arterial inflammation and destabilization of atherosclerotic plaque. Eur Heart J. 2015. doi:10.1093/eurheartj/ehv653. This article summarizes the concept of plaque rupture related to cholesterol crystallization.

    PubMed  Google Scholar 

  15. 15.

    Muller JE, Abela GS, Nesto RW, Tofler GH. Triggers, acute risk factors, and vulnerable plaques: the lexicon of a new frontier. J Am Coll Cardiol. 1994;23:809–13.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Schaar JA, Muller JE, Falk E, Virmani R, Fuster V, Serruys PW, et al. Terminology for high-risk and vulnerable coronary artery plaques. Report of a meeting on the vulnerable plaque, June 17 and 18, 2003, Santorini, Greece. Eur Heart J. 2004;25:1077–82.

    Article  PubMed  Google Scholar 

  17. 17.

    Watanabe Y. Serial inbreeding of rabbits with hereditary hyperlipidemia (WHHL rabbit). Incidence and development of atherosclerosis and xanthoma. Atherosclerosis. 1980;36:261–8.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Pundziute G, Schuijf JD, Jukema JW, Decramer I, Sarno G, Vanhoenacker PK, et al. Evaluation of plaque characteristics in acute coronary syndromes: non-invasive assessment with multi-slice computed tomography and invasive evaluation with intravascular ultrasound radiofrequency data analysis. Eur Heart J. 2008;29:2373–81.

    Article  PubMed  Google Scholar 

  19. 19.

    Baumgartner HR, Studer A. Folgen des Geffasskatheterismus am hypercholesterinaemischen Kaninchen. Pathol Microbiol. 1966;29:393–405.

    CAS  Google Scholar 

  20. 20.

    Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288:373–6.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Khadshadurian AK. The inheritance of essential familial hypercholesterolemia. Am J Med. 1964;37:402–7.

    Article  Google Scholar 

  22. 22.

    Brown MS, Goldstein JL. Receptor-mediated endocytosis: insights from the lipoprotein receptor system. Proc Natl Acad Sci U S A. 1979;76:3330–7.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Goldstein JL, Brown MS. The LDL receptor. Arterioscler Thromb Vasc Biol. 2009;29:431–8.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34:154–6.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Shiomi M, Ito T, Yamada S, Kawashima S, Fan J. Development of an animal model for spontaneous myocardial infarction (WHHLMI rabbit). Arterioscler Thromb Vasc Biol. 2003;23:1239–44.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Shiomi M, Ito T. The Watanabe heritable hyperlipidemic (WHHL) rabbit, its characteristics and history of development: a tribute to the late Dr. Yoshio Watanabe. Atherosclerosis. 2009;207:1–7.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Watanabe Y, Ito T, Saeki M, Kuroda M, Tanzawa K, Mochizuki M, et al. Hypolipidemic effects of CS-500 (ML-236B) in WHHL-rabbit, a heritable animal model for hyperlipidemia. Atherosclerosis. 1981;38:27–31.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Watanabe Y, Ito T, Shiomi M, Tsujita Y, Kuroda M, Arai M, et al. Preventive effect of pravastatin sodium, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on coronary atherosclerosis and xanthoma in WHHL rabbits. Biochim Biophys Acta. 1988;960:294–302.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Shiomi M, Ito T, Tsukada T, Yata T, Watanabe Y, Tsujita Y, et al. Reduction of serum cholesterol levels alters lesional composition of atherosclerotic plaques. Effect of pravastatin sodium on atherosclerosis in mature WHHL rabbits. Arterioscler Thromb Vasc Biol. 1995;15:1938–44.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Fukumoto Y, Libby P, Rabkin E, Hill CC, Enomoto M, Hirouchi Y, et al. Statins alter smooth muscle cell accumulation and collagen content in established atheroma of watanabe heritable hyperlipidemic rabbits. Circulation. 2001;103:993–9.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Shiomi M, Ito T, Hirouchi Y, Enomoto M. Fibromuscular cap composition is important for the stability of established atherosclerotic plaques in mature WHHL rabbits treated with statins. Atherosclerosis. 2001;157:75–84.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Haudenschild C, Studer A. Early interactions between blood cells and severely damaged rabbit aorta. Eur J Clin Investig. 1971;2:1–7.

    CAS  Article  Google Scholar 

  33. 33.

    Faxon DP, Balelli LA, Sandborn T, Haudenschild C, Valeri R, Ryan TJ. The effect of antiplatelet therapy on platelet accumulartion after experimental angioplasty in the rabbit iliac model. Int J Cardiol. 1992;36:41–7.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Block PC, Baughman KL, Pasternak RC, Fallon JT. Transluinal angioplasty: correlation of morphologic and angiographic findings in an experimental model. Circulation. 1980;61:778–85.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Sanborn T, Faxon DP, Haudenschild C, Gottsman SB, Ryan TJ. The mechanism of transluminal angioplasty: evidence for formation of aneurysm in experimental atherosclerosis. Circulation. 1983;68:1136–40.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Post MJ, Kuntz RE, Borst C. Remodeling after PTCA: from shrinkage to compensatory enlargement. Circulation. 1995;92:2002–3.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Abela GS, Normann SJ, Cohen DM, Franzini D, Feldman RL, Crea F, et al. Laser recanalization of occluded atherosclerotic arteries in vivo and in vitro. Circulation. 1985;71:403–11.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Sanborn TA, Haudenschild CC, Garber GR, Ryan TJ, Faxon DP. Angiographic and histologic consequences of laser thermal angioplasty: comparison with balloon angioplasty. Circulation. 1987;75:1281–6.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Iqbal J, Chamberlain J, Francis S, Gunn J. Role of animal models in coronary stenting. Ann Biomed Eng. 2015. doi:10.1007/s10439-015-1414-4.

    PubMed  Google Scholar 

  40. 40.

    Waksman R, McEwan P, Moore T, Pakala R, Kolodgie F, Hellinga D. PhotoPoint photodynamic therapy promotes stabilization of atherosclerotic plaques and inhibits plaque progression. J Am Coll Cardiol. 2008;52:1024–32.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Aikawa M, Voglic SJ, Sugiyama S, Rabkin E, Taubman MB, Fallon JT, et al. Dietary lipid lowering reduces tissue factor expression in rabbit atheroma. Circulation. 1999;100:1215–22.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Runge RS, Haber E. Animal models for the study of thrombolysis in vivo. Circulation. 1991;83(suppl IV):IV–IV2.

    Google Scholar 

  43. 43.

    Priyadharsini RP. Animal models to evaluate anti-atherosclerotic drugs. Fundam Clin Pharmacol. 2015;29:329–40.

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Constantinides P, Booth J, Carlson G. Production of advanced cholesterol atherosclerosis in the rabbit. Arch Pathol. 1960;70:80–92.

    Google Scholar 

  45. 45.•

    Abela GS, Picon PD, Friedl SE, Gebara OC, Federman M, Tofler GH, et al. Triggering of plaque disruption and arterial thrombosis in an atherosclerotic rabbit model. Circulation. 1995;91:776–84. This describes the modified model of plaque rupture and thrombosis in the atherosclerotic rabbit model.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Tanaka H, Sukhova GK, Swanson SJ, Clinton SK, Ganz P, Cybulsky MI, et al. Sustained activation of vascular cells and leukocytes in the rabbit aorta after balloon injury. Circulation. 1993;88:1788–803.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Phinikaridou A, Hallock KJ, Qiao Y, Hamilton JA. A robust rabbit model of human atherosclerosis and atherothrombosis. J Lipid Res. 2009;50:787–97.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Johnstone MT, Botnar RM, Perez AS, Stewart R, Quist WC, Hamilton JA, et al. In vivo magnetic resonance imaging of experimental thrombosis in a rabbit model. Arterioscler Thromb Vasc. 2001;21:1556–60.

    CAS  Article  Google Scholar 

  49. 49.

    Viereck J, Ruberg FL, Qiao Y, Perez AS, Detwiller K, Johnstone M, et al. MRI of atherothrombosis associated with plaque rupture. Arterioscler Thromb Vasc Biol. 2005;25:240–5.

    CAS  PubMed  Google Scholar 

  50. 50.

    Phinikaridou A, Ruberg FL, Hallock KJ, Qiao Y, Hua N, Viereck J, et al. In vivo detection of vulnerable atherosclerotic plaque by MRI in a rabbit model. Circ Cardiovasc Imaging. 2010;3:323–32.

    Article  PubMed  Google Scholar 

  51. 51.

    Pham T, Hua N, Phinikaridou A, Killiany R, Hamilton J. Early in vivo discrimination of vulnerable atherosclerotic plaques that disrupt: a serial MRI study. Atherosclerosis. 2016;244:101–7.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Hua N, Baik F, Pham T, Phinikaridou A, Giordano N, Friedman B, et al. Identification of high-risk plaques by MRI and fluorescence imaging in a rabbit model of atherothrombosis. PLoS One. 2015;10, e0139833. doi:10.1371/journal.pone.0139833.

    Article  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Li H, El-Dakdouki MH, Zhu DC, Abela GS, Huang X. Synthesis of ß-Cyclodextrin conjugated superparamagnetic iron oxide nanoparticles for selective binding and detection of cholesterol crystals. Chem Commun. 2012;48:3385–7.

    CAS  Article  Google Scholar 

  54. 54.

    El-Dakdouki MH, El-Boubbou K, Kamat M, Huang R, Abela GS, Kiupel M, et al. CD44 targeting magnetic glyconanoparticles for atherosclerotic plaque imaging. Pharm Res. 2014;31:1426–37.

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Aziz K, Berger K, Claycombe K, Huang R, Patel R, Abela GS. Non-Invasive detection and localization of vulnerable plaque and arterial thrombosis using CTA/PET. Circulation. 2008;117:2061–70.

    Article  PubMed  Google Scholar 

  56. 56.

    Rudd JH, Narula J, Strauss HW, Virmani R, Machac J, Klimas M. Imaging atherosclerotic plaque inflammation by fluorodeoxyglucose with positron emission tomography: ready for prime time? J Am Coll Cardiol. 2010;55:2527–35.

    Article  PubMed  Google Scholar 

  57. 57.••

    Patel R, Janoudi A, Vedre A, Aziz K, Tamhane U, Rubinstein J, et al. Plaque rupture and thrombosis is reduced by lowering cholesterol levels and crystallization with ezetimibe and is correlated with FDG-PET. Arterioscler Thromb Vasc Biol. 2007;31:2007–14. This article is critical in demonstrating how cholesterol crystals form very early in atherosclerosis and also develop thrombosis at sites of heavy crystal deposits.

    Article  Google Scholar 

  58. 58.

    Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387–97.

    CAS  Article  PubMed  Google Scholar 

  59. 59.•

    Abela GS, Aziz K, Vedre A, Pathak D, Talbott JD, DeJong J. Effect of cholesterol crystals on plaques and intima in arteries of patients with acute coronary and cerebrovascular syndromes. Am J Cardiol. 2009;103:959–68. This is a landmark report of cholesterol crystals perforating the intimal surface at sites of plaque rupture in humans who died with myocardial infarction.

    CAS  Article  PubMed  Google Scholar 

  60. 60.

    Liu L, Gardecki JA, Nadkarni SK, Toussaint JD, Yagi Y, Bouma BE, et al. Imaging the subcellular structure of human coronary atherosclerosis using micro–optical coherence tomography. Nat Med. 2011;17:1010–4.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  61. 61.••

    Abela GS, Aziz K. Cholesterol crystals rupture biological membranes and human plaques during acute cardiovascular events: a novel insight into plaque rupture by scanning electron microscopy. Scanning. 2006;28:1–10. This is the initial report demonstrating the how cholesterol crystals perforate fibrous membranes as they grow and also showed the first human case of crystals perforating the intima of the coronary artery.

    CAS  Article  PubMed  Google Scholar 

  62. 62.

    Goldstein JA. Multifocal coronary plaque instability. Prog Cardiovasc Dis. 2002;44:449–54.

    Article  PubMed  Google Scholar 

  63. 63.

    Abela GS, Eisenberg JD. Plaque disruption and thrombosis: models to evaluate acute cardiovascular events. In: Becker RC, editor. Textbook of coronary thrombosis and thrombolysis. Boston: Kluwer; 1998. p. 207–17.

    Google Scholar 

  64. 64.

    Naghavi M, Libby P, Falk E, Casscells W, Litovsky S, Rumberger J, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation. 2003;108:1664–72.

    Article  PubMed  Google Scholar 

  65. 65.

    Abela GS, Aziz K. Cholesterol crystals cause mechanical damage to biological membranes: a proposed mechanism of plaque rupture and erosion leading to arterial thrombosis. Clin Cardiol. 2005;28:413–20.

    Article  PubMed  Google Scholar 

  66. 66.

    Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440:237–41.

    CAS  Article  PubMed  Google Scholar 

  67. 67.

    Ma H, Aziz KS, Huang R, Abela GS. Arterial wall cholesterol content is a predictor of development and severity of arterial thrombosis. J Thromb Thrombolysis. 2006;22:5–11.

    CAS  Article  PubMed  Google Scholar 

  68. 68.

    Tian J, Ren X, Vergallo R, Xing L, Yu H, Jia H, et al. Distinct morphological features of ruptured culprit plaque for acute coronary events compared to those with silent rupture and thin-cap fibroatheroma: a combined optical coherence tomography and intravascular ultrasound study. J Am Coll Cardiol. 2014;63:2209–16.

    Article  PubMed  Google Scholar 

  69. 69.

    Katz SS, Shipley GG, Small DM. Physical chemistry of the lipids of human atherosclerotic lesions. Demonstration of a lesion intermediate between fatty streaks and advanced plaques. J Clin Invest. 1976;58:200–11.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  70. 70.

    Lundberg B. Chemical composition and physical state of lipid deposits in atherosclerosis. Atherosclerosis. 1985;56:93–110.

    CAS  Article  PubMed  Google Scholar 

  71. 71.

    Guo W, Morrisett JD, DeBakey ME, Lawrie GM, Hamilton JA. Quantification in situ of crystalline cholesterol and calcium phosphate hydroxyapatite in human atherosclerotic plaques by solid-state magic angle spinning NMR. Arterioscler Thromb Vasc Biol. 2000;20:1630–6.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Vedre A, Pathak DR, Crimp M, Lum C, Koochesfahani M, Abela GS. Physical factors that trigger cholesterol crystallization leading to plaque rupture. Atherosclerosis. 2009;203:89–96.

    CAS  Article  PubMed  Google Scholar 

  73. 73.

    Nasiri M, Huang R, Janoudi A, Vanderberg A, Flegler C, Flegler S, et al. Unraveling the role of cholesterol crystals in plaque rupture by altering the method of tissue preparation. Microsc Res Tech. 2015;78:969–74.

    CAS  Article  PubMed  Google Scholar 

  74. 74.

    Abela GS, Vedre A, Janoudi A, Huang R, Durga S, Tamhane U. Effect of statins on cholesterol crystallization and atherosclerotic plaque stabilization. Am J Cardiol. 2011;107:1710–7.

    CAS  Article  PubMed  Google Scholar 

  75. 75.

    Patti G, Pasceri V, Colonna G, Miglionico M, Fischetti D, Sardella G, et al. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. J Am Coll Cardiol. 2007;49:1272–8.

    CAS  Article  PubMed  Google Scholar 

  76. 76.

    Fernandez-Jarne E, Martinez-Losa E, Serrano-Martinez M, Prado-Santamaria M, Brugarolas-Brufau C, Martinez-Gonzalez MA. Type of alcoholic beverage and first acute myocardial infarction: a case–control study in a Mediterranean country. Clin Cardiol. 2003;26:313–8.

    CAS  Article  PubMed  Google Scholar 

  77. 77.

    Bulgarelli A, Martins Dias AA, Caramelli B, Maranhão RC. Treatment with methotrexate inhibits atherogenesis in cholesterol-fed rabbits. J Cardiovasc Pharmacol. 2012;59:308–14.

    CAS  Article  PubMed  Google Scholar 

  78. 78.

    Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013;61:404–10.

    CAS  Article  PubMed  Google Scholar 

  79. 79.

    Everett BM, Pradhan AD, Solomon DH, Paynter N, Macfadyen J, Zaharris E, et al. Rationale and design of the Cardiovascular Inflammation Reduction Trial: a test of the inflammatory hypothesis of atherothrombosis. Am Heart J. 2013;166:199–207.

    Article  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1b inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162:597–605.

    CAS  Article  PubMed  Google Scholar 

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Correspondence to George S. Abela.

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Conflict of Interest

Oliver G. Abela, Fadi Alreefi, Negar Salehi, Imran Baig, and Abed Janoudi declare that they have no conflict of interest.

Chowdhury H. Ahsan declares personal fees from AstraZeneca, Amgen, and Boehringer Ingelheim for serving as a speaker.

George S. Abela declares personal and grant fees and nonfinancial support from Merck, as well as personal fees and non-financial support from Amgen, Daiichi Sankyo, and Kowa Pharmaceuticals.

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Abela, O.G., Ahsan, C.H., Alreefi, F. et al. Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism. Curr Atheroscler Rep 18, 29 (2016).

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  • Cholesterol crystals
  • Inflammation
  • Atherosclerosis
  • Plaque rupture
  • Rabbit model