Download PDF
CC BY 4.0 · Aorta (Stamford) 2013; 01(05): 244-254
DOI: 10.12945/j.aorta.2013.13-052
State-of-the-Art Review
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Lessons from Animal Models of Arterial Aneurysm

S. David Gertz
1   Institute for Medical Research (IMRIC), Faculty of Medicine, The Hebrew University of Jerusalem and Hadassah University Hospital, Jerusalem, Israel
,
Yoav Mintz
1   Institute for Medical Research (IMRIC), Faculty of Medicine, The Hebrew University of Jerusalem and Hadassah University Hospital, Jerusalem, Israel
,
Ronen Beeri
1   Institute for Medical Research (IMRIC), Faculty of Medicine, The Hebrew University of Jerusalem and Hadassah University Hospital, Jerusalem, Israel
,
Chen Rubinstein
1   Institute for Medical Research (IMRIC), Faculty of Medicine, The Hebrew University of Jerusalem and Hadassah University Hospital, Jerusalem, Israel
,
Dan Gilon
1   Institute for Medical Research (IMRIC), Faculty of Medicine, The Hebrew University of Jerusalem and Hadassah University Hospital, Jerusalem, Israel
,
Leah Gavish
1   Institute for Medical Research (IMRIC), Faculty of Medicine, The Hebrew University of Jerusalem and Hadassah University Hospital, Jerusalem, Israel
,
Yacov Berlatzky
1   Institute for Medical Research (IMRIC), Faculty of Medicine, The Hebrew University of Jerusalem and Hadassah University Hospital, Jerusalem, Israel
,
Liat Appelbaum
1   Institute for Medical Research (IMRIC), Faculty of Medicine, The Hebrew University of Jerusalem and Hadassah University Hospital, Jerusalem, Israel
,
Lilach Gavish
1   Institute for Medical Research (IMRIC), Faculty of Medicine, The Hebrew University of Jerusalem and Hadassah University Hospital, Jerusalem, Israel
› Author Affiliations
Further Information

Publication History

17 October 2013

30 October 2013

Publication Date:
28 September 2018 (online)

   Permissions and Reprints

Abstract

We review the results from the most common animal models of arterial aneurysm, including recent findings from our novel, laparoscopy-based pig model of abdominal aortic aneurysm, that contribute important insights into early pathogenesis. We emphasize the relevance of these findings for evaluation of treatment protocols and novel device prototypes for mechanism-based prevention of progression and rupture.

Key Words

Abdominal aortic aneurysm - Arterial aneurysm - Animal models - Periarterial calcium chloride
 

  • References

  • 1 U.S. Preventive Services Task Force. Screening for abdominal aortic aneurysm: recommendation statement. Ann Intern Med 2005; 142: 198-202 . 10.7326/0003-4819-142-3-200502010-00011
    PubMedGoogle Scholar
  • 2 Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB. , et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation 2012; 125: e2-e220 . 10.1161/CIR.0b013e31823ac046
    CrossrefPubMedGoogle Scholar
  • 3 Nordon IM, Hinchliffe RJ, Loftus IM, Thompson MM. Pathophysiology and epidemiology of abdominal aortic aneurysms. Nat Rev Cardiol 2010; 8: 92-102 . 10.1038/nrcardio.2010.180
    CrossrefPubMedGoogle Scholar
  • 4 Baxter BT, Terrin MC, Dalman RL. Medical management of small abdominal aortic aneurysms. Circulation 2008; 117: 1883-1889 . 10.1161/CIRCULATIONAHA.107.735274
    CrossrefPubMedGoogle Scholar
  • 5 Thompson RW. Reflections on the pathogenesis of abdominal aortic aneurysms. Cardiovasc Surg 2002; 10: 389-394 . 10.1016/S0967-2109(02)00042-X
    CrossrefPubMedGoogle Scholar
  • 6 Drury D, Michaels JA, Jones L, Ayiku L. Systematic review of recent evidence for the safety and efficacy of elective endovascular repair in the management of infrarenal abdominal aortic aneurysm. Br J Surg 2005; 92: 937-946 . 10.1002/bjs.5123
    CrossrefPubMedGoogle Scholar
  • 7 Wilt TJ, Lederle FA, Macdonald R, Jonk YC, Rector TS, Kane RL. Comparison of endovascular and open surgical repairs for abdominal aortic aneurysm. Evid Rep Technol Assess (Full Rep) 2006; 1-113
    PubMedGoogle Scholar
  • 8 Gertz SD, Kurgan A, Eisenberg D. Aneurysm of the rabbit common carotid artery induced by periarterial application of calcium chloride in vivo. J Clin Invest 1988; 81: 649-656 . 10.1172/JCI113368
    CrossrefPubMedGoogle Scholar
  • 9 Gertz SD. Vascular damage and thrombosis from spasm. N Engl J Med 1979; 300: 197 . 10.1056/NEJM197901253000413
    PubMedGoogle Scholar
  • 10 Joris I, Majno G. Endothelial changes induced by arterial spasm. Am J Pathol 1981; 102: 346-358
    PubMedGoogle Scholar
  • 11 Gertz SD, Uretsky G, Wajnberg RS, Navot N, Gotsman MS. Endothelial cell damage and thrombus formation after partial arterial constriction: relevance to the role of coronary artery spasm in the pathogenesis of myocardial infarction. Circulation 1981; 63: 476-486 . 10.1161/01.CIR.63.3.476
    CrossrefPubMedGoogle Scholar
  • 12 Blaumanis OR, Gertz SD, Grady PA, Nelson E. Thrombosis in acute experimental cerebral vasospasm. The Joint Meeting on Stroke and Cerebral Circulation, Dallas, Texas. Stroke 1976; 7: 9-10
    PubMedGoogle Scholar
  • 13 Blaumanis OR, Grady PA, Nelson E. Hemodynamic and morphological aspects of cerebral vasospasm. In: Price TR, Nelson E. , editors. Cerebrovascular Diseases. New York: Raven Press; 1979. pp. 283-294
    Google Scholar
  • 14 Marzilli M, Goldstein S, Trivella MG, Palumbo C, Maseri A. Some clinical considerations regarding the relation of coronary vasospasm to coronary atherosclerosis: a hypothetical pathogenesis. Am J Cardiol 1980; 45: 882-886 . 10.1016/0002-9149(80)90135-6
    CrossrefPubMedGoogle Scholar
  • 15 Kurgan A, Gertz SD, Wajnberg RS. Intimal changes associated with arterial spasm induced by periarterial application of calcium chloride. Exp Mol Pathol 1983; 39: 176-193 . 10.1016/0014-4800(83)90050-3
    CrossrefPubMedGoogle Scholar
  • 16 Chiou AC, Chiu B, Pearce WH. Murine aortic aneurysm produced by periarterial application of calcium chloride. J Surg Res 2001; 99: 371-376 . 10.1006/jsre.2001.6207
    CrossrefPubMedGoogle Scholar
  • 17 Longo GM, Xiong W, Greiner TC, Zhao Y, Fiotti N, Baxter BT. Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. J Clin Invest 2002; 110: 625-632 . 10.1172/JCI15334
    CrossrefPubMedGoogle Scholar
  • 18 Ikonomidis JS, Gibson WC, Gardner J, Sweterlitsch S, Thompson RP, Mukherjee R. , et al. A murine model of thoracic aortic aneurysms. J Surg Res 2003; 115: 157-163 . 10.1016/S0022-4804(03)00193-8
    CrossrefPubMedGoogle Scholar
  • 19 Geng L, Wang W, Chen Y, Cao J, Lu L, Chen Q. , et al. Elevation of ADAM10, ADAM17, MMP-2 and MMP-9 expression with media degeneration features CaCl2-induced thoracic aortic aneurysm in a rat model. Exp Mol Pathol 2010; 89: 72-81 . 10.1016/j.yexmp.2010.05.006
    CrossrefPubMedGoogle Scholar
  • 20 Wang Y, Krishna S, Golledge J. The calcium chloride-induced rodent model of abdominal aortic aneurysm. Atherosclerosis 2013; 226: 29-39 . 10.1016/j.atherosclerosis.2012.09.010
    CrossrefPubMedGoogle Scholar
  • 21 Anidjar S, Salzmann JL, Gentric D, Lagneau P, Camilleri JP, Michel JB. Elastase-induced experimental aneurysms in rats. Circulation 1990; 82: 973-981 . 10.1161/01.CIR.82.3.973
    CrossrefPubMedGoogle Scholar
  • 22 Anidjar S, Dobrin PB, Eichorst M, Graham GP, Chejfec G. Correlation of inflammatory infiltrate with the enlargement of experimental aortic aneurysms. J Vasc Surg 1992; 16: 139-147 . 10.1067/mva.1992.35585
    CrossrefPubMedGoogle Scholar
  • 23 Pyo R, Lee JK, Shipley JM, Curci JA, Mao D, Ziporin SJ. , et al. Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms. J Clin Invest 2000; 105: 1641-1649 . 10.1172/JCI8931
    CrossrefPubMedGoogle Scholar
  • 24 Yamaguchi T, Yokokawa M, Suzuki M, Higashide S, Katoh Y, Sugiyama S. , et al. Morphologic changes in the aorta during elastase infusion in the rat aneurysm model. J Surg Res 2001; 95: 161-166 . 10.1006/jsre.2000.6025
    CrossrefPubMedGoogle Scholar
  • 25 Kallmes DF, Fujiwara NH, Berr SS, Helm GA, Cloft HJ. Elastase-induced saccular aneurysms in rabbits: a dose-escalation study. AJNR Am J Neuroradiol 2002; 23: 295-298
    PubMedGoogle Scholar
  • 26 White JV, Mazzacco SL. Formation and growth of aortic aneurysms induced by adventitial elastolysis. Ann N Y Acad Sci 1996; 800: 97-120 . 10.1111/j.1749-6632.1996.tb33302.x
    CrossrefPubMedGoogle Scholar
  • 27 Origuchi N, Shigematsu H, Izumiyama N, Nakamura K, Toku A, Muto T. Aneurysm induced by periarterial application of elastase heals spontaneously. Int Angiol 1998; 17: 113-119
    PubMedGoogle Scholar
  • 28 Tanaka A, Hasegawa T, Chen Z, Okita Y, Okada K. A novel rat model of abdominal aortic aneurysm using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure. J Vasc Surg 2009; 50: 1423-1432 . 10.1016/j.jvs.2009.08.062
    CrossrefPubMedGoogle Scholar
  • 29 Bi Y, Zhong H, Xu K, Zhang Z, Qi X, Xia Y. , et al. Development of a novel rabbit model of abdominal aortic aneurysm via a combination of periaortic calcium chloride and elastase incubation. PLoS One 2013; 8: e68476 . 10.1371/journal.pone.0068476
    CrossrefPubMedGoogle Scholar
  • 30 Yamawaki-Ogata A, Hashizume R, Satake M, Kaneko H, Mizutani S, Moritan T. , et al. A doxycycline loaded, controlled-release, biodegradable fiber for the treatment of aortic aneurysms. Biomaterials 2010; 31: 9554-9564 . 10.1016/j.biomaterials.2010.08.069
    CrossrefPubMedGoogle Scholar
  • 31 Dodd BR, Spence RA. Doxycycline inhibition of abdominal aortic aneurysm growth: a systematic review of the literature. Curr Vasc Pharmacol 2011; 9: 471-478 . 10.2174/157016111796197288
    CrossrefPubMedGoogle Scholar
  • 32 Daugherty A, Manning MW, Cassis LA. Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice. J Clin Invest 2000; 105: 1605-1612 . 10.1172/JCI7818
    CrossrefPubMedGoogle Scholar
  • 33 Saraff K, Babamusta F, Cassis LA, Daugherty A. Aortic dissection precedes formation of aneurysms and atherosclerosis in angiotensin II-infused, apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2003; 23: 1621-1626 . 10.1161/01.ATV.0000085631.76095.64
    CrossrefPubMedGoogle Scholar
  • 34 Daugherty A, Cassis LA. Mouse models of abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol 2004; 24: 429-434 . 10.1161/01.ATV.0000118013.72016.ea
    CrossrefPubMedGoogle Scholar
  • 35 Barisione C, Charnigo R, Howatt DA, Moorleghen JJ, Rateri DL, Daugherty A. Rapid dilation of the abdominal aorta during infusion of angiotensin II detected by noninvasive high-frequency ultrasonography. J Vasc Surg 2006; 44: 372-376 . 10.1016/j.jvs.2006.04.047
    CrossrefPubMedGoogle Scholar
  • 36 Cassis LA, Gupte M, Thayer S, Zhang X, Charnigo R, Howatt DA. , et al. ANG II infusion promotes abdominal aortic aneurysms independent of increased blood pressure in hypercholesterolemic mice. Am J Physiol Heart Circ Physiol 2009; 296: H1660-H1665
    CrossrefPubMedGoogle Scholar
  • 37 Bruemmer D, Daugherty A, Lu H, Rateri DL. Relevance of angiotensin II-induced aortic pathologies in mice to human aortic aneurysms. Ann N Y Acad Sci 2011; 1245: 7-10 . 10.1111/j.1749-6632.2011.06332.x
    CrossrefPubMedGoogle Scholar
  • 38 Gavish L, Rubinstein C, Berlatzky Y, Gavish LY, Beeri R, Gilon D. , et al. Low level laser arrests abdominal aortic aneurysm by collagen matrix reinforcement in apolipoprotein E-deficient mice. Lasers Surg Med 2012; 44: 664-674 . 10.1002/lsm.22068
    CrossrefPubMedGoogle Scholar
  • 39 Lindsay ME, Dietz HC. Lessons on the pathogenesis of aneurysm from heritable conditions. Nature 2011; 473: 308-316 . 10.1038/nature10145
    CrossrefPubMedGoogle Scholar
  • 40 Barnett BD, Bird HR, Lalich JJ, Strong FM. Toxicity of beta-amino-propionitrile for turkey poults. Proc Soc Exp Biol Med 1957; 94: 67-70 . 10.3181/00379727-94-22857
    CrossrefPubMedGoogle Scholar
  • 41 Simpson CF, Kling JM, Robbins RC, Harms RH. Beta-aminopropionitrile-induced aortic ruptures in turkeys: inhibition by reserpine and enhancement by monoamine oxidase inhibitors. Toxicol Appl Pharmacol 1968; 12: 48-59 . 10.1016/0041-008X(68)90175-0
    CrossrefPubMedGoogle Scholar
  • 42 Simpson CF, Boucek RJ. The B-aminopropionitrile-fed turkey: a model for detecting potential drug action on arterial tissue. Cardiovasc Res 1983; 17: 26-32 . 10.1093/cvr/17.1.26
    CrossrefPubMedGoogle Scholar
  • 43 Rowe DW, McGoodwin EB, Martin GR, Grahn D. Decreased lysyl oxidase activity in the aneurysm-prone, mottled mouse. J Biol Chem 1977; 252: 939-942
    PubMedGoogle Scholar
  • 44 Brophy C, Tilson JE, Tilson MD. Propranolol delays the formation of aneurysms in the male blotchy mouse. J Surg Res 1988; 44: 687-689 . 10.1016/0022-4804(88)90101-1
    CrossrefPubMedGoogle Scholar
  • 45 Brophy CM, Tilson JE, Tilson MD. Propranolol stimulates the crosslinking of matrix components in skin from the aneurysm-prone blotchy mouse. J Surg Res 1989; 46: 330-332 . 10.1016/0022-4804(89)90197-2
    CrossrefPubMedGoogle Scholar
  • 46 Marinov GR, Marois Y, Pâris E, Roby P, Formichi M, Douville Y. , et al. Can the infusion of elastase in the abdominal aorta of the Yucatán miniature swine consistently produce experimental aneurysms?. J Invest Surg 1997; 10: 129-150 . 10.3109/08941939709032144
    CrossrefPubMedGoogle Scholar
  • 47 Sadek M, Hynecek RL, Goldenberg S, Kent KC, Marin ML, Faries PL. Gene expression analysis of a porcine native abdominal aortic aneurysm model. Surgery 2008; 144: 252-258 . 10.1016/j.surg.2008.04.007
    CrossrefPubMedGoogle Scholar
  • 48 Hynecek RL, DeRubertis BG, Trocciola SM, Zhang H, Prince MR, Ennis TL. , et al. The creation of an infrarenal aneurysm within the native abdominal aorta of swine. Surgery 2007; 142: 143-149 . 10.1016/j.surg.2007.04.014
    CrossrefPubMedGoogle Scholar
  • 49 Czerski A, Bujok J, Gnus J, Hauzer W, Ratajczak K, Nowak M. , et al. Experimental methods of abdominal aortic aneurysm creation in swine as a large animal model. J Physiol Pharmacol 2013; 64: 185-192
    PubMedGoogle Scholar
  • 50 Molácek J, Treska V, Kobr J, Certík B, Skalický T, Kuntscher V. , et al. Optimization of the model of abdominal aortic aneurysm–experiment in an animal model. J Vasc Res 2009; 46: 1-5 . 10.1159/000135659
    PubMedGoogle Scholar
  • 51 Lin PY, Wu YT, Lin GC, Shih YH, Sampilvanjil A, Chen LR. , et al. Coarctation-induced degenerative abdominal aortic aneurysm in a porcine model. J Vasc Surg 2013; 57: 806-815.e1 . 10.1016/j.jvs.2012.08.104
    CrossrefPubMedGoogle Scholar
  • 52 Usón-Gargallo J, Crisóstomo V, Loscertales B, Sun F, Sánchez-Margallo FM, Martín-Cancho MF. , et al. A new model of abdominal aortic aneurysm with gastric serosa patch: surgical technique and short-term evaluation. J Invest Surg 2006; 19: 97-104 . 10.1080/08941930600569415
    CrossrefPubMedGoogle Scholar
  • 53 Diaz S, Uzieblo MR, Desai KM, Talcott MR, Bae KT, Geraghty PJ. , et al. Type II endoleak in porcine model of abdominal aortic aneurysm. J Vasc Surg 2004; 40: 339-344 . 10.1016/j.jvs.2004.04.003
    CrossrefPubMedGoogle Scholar

    • References

    • 1 Kuivaniemi H, Platsoucas CD, Tilson MD. Aortic aneurysms: an immune disease with a strong genetic component. Circulation 2008; 117: 242-252 . 10.1161/FCIRCULATIONAHA.107.690982
      CrossrefPubMedGoogle Scholar
    • 2 Rizas KD, Ippagunta N, Tilson MD. Immune cells and molecular mediators in the pathogenesis of the abdominal aortic aneurysm. Cardiol Rev 2009; 17: 201-210 . 10.1097/CRD.0b013e3181b04698
      Google Scholar
    • 3 Suh JH, Yoon JS, Kim HW, Jo KH. Adventitial fibroblast abnormality in thoracic aortic aneurysms and aortic dissections. Korean J Thorac Cardiovasc Surg 2011; 44: 406-412 . 10.5090/kjtcs.2011.44.6.406
      CrossrefPubMedGoogle Scholar
    • 4 Halpern VJ, Nackman GB, Gandhi RH, Irizarry E, Scholes JV, Ramey WG. , et al. The elastase infusion model of experimental aortic aneurysms: synchrony of induction of endogenous proteinases with matrix destruction and inflammatory cell response. J Vasc Surg 1994; 20: 51-60 . 10.1016/0741-5214(94)90175-9
      CrossrefPubMedGoogle Scholar
    • 5 Luo J, Fujikura K, Tyrie LS, Tilson MD, Konofagou EE. Pulse wave imaging of normal and aneurismal abdominal aortas in vivo. IEE Trans Med Imaging 2009; 28: 477-486 . 10.1109/TMI.2008.928179
      PubMedGoogle Scholar
    • 6 Gorilla heart disease deaths puzzling zoos. Los Angeles Times. April 9, 2008
      PubMedGoogle Scholar
    • 7 Kenny DE, Cambre RC, Alvarado TP, Prowten AW, Allchurch AF, Marks SK. , et al. Aortic dissection: an important cardiovascular disease in captive gorillas (Gorilla gorilla gorilla). J Zoo Wildlife Med 1994; 25: 561-568 . 10.1016/S0967-2109(02)00140-0
      PubMedGoogle Scholar