Background The purpose of this study was to introduce a novel, simple and effective technique for creating a reliable rabbit model of abdominal aortic aneurysm (AAA) via a combination of periaortic calcium chloride (CaCl2) and elastase incubation. Methods Forty-eight New Zealand white rabbits were divided into four groups. The AAA model was developed via a 20-minute periaortic incubation of CaCl2 (0.5 mol/L) and elastase (1 Unit/μL) in a 1.5-cm aortic segment (Group CE). A single incubation of CaCl2 (Group C) or elastase (Group E) and a sham operation group (Sham Group) were used for the controls. Diameter was measured by serial digital subtraction angiography imaging on days 5, 15 and 30. Animals were sacrificed on day 5 and day 30 for histopathological and immunohistochemical studies. Results All animals in Group CE developed aneurysm, with an average dilation ratio of 65.3%±8.9% on day 5, 86.5%±28.7% on day 15 and 203.6%±39.1% on day 30. No aneurysm was found in Group C, and only one aneurysm was seen on day 5 in Group E. Group CE exhibited less intima-media thickness, endothelial recovery, elastin and smooth muscle cell (SMC) content, but stronger expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and RAM11 compared to the controls. Conclusions The novel rabbit model of AAA created by using a combination of periaortic CaCl2 and elastase incubation is simple and effective to perform and is valuable for elucidating AAA mechanisms and therapeutic interventions in experimental studies.
References
[1]
Ernst CB (1993) Abdominal aortic aneurysm. N Engl J Med 328: 1167–1172.
[2]
Shimizu K MR, Mitchell RN, Libby P (2006) Inflammation and cellular immune responses in abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol 26: 987–994.
Miskolczi L, Guterman LR, Flaherty JD, Hopkins LN (1998) Saccular aneurysm induction by elastase digestion of the arterial wall: a new animal model. Neurosurgery 43: 595–600; discussion 600–591.
[6]
Sasaki K, Ujiie H, Higa T, Hori T, Shinya N, et al. (2004) Rabbit aneurysm model mediated by the application of elastase. Neurol Med Chir (Tokyo) 44: 467–473.
[7]
Yasuda H, Kuroda S, Nanba R, Ishikawa T, Shinya N, et al. (2005) A novel coating biomaterial for intracranial aneurysms: effects and safety in extra- and intracranial carotid artery. Neuropathology 25: 66–76.
[8]
Miyake T, Aoki M, Masaki H, Kawasaki T, Oishi M, et al. (2007) Regression of abdominal aortic aneurysms by simultaneous inhibition of nuclear factor kappaB and ets in a rabbit model. Circ Res 101: 1175–1184.
[9]
Origuchi N, Shigematsu H, Izumiyama N, Nakamura K, Toku A, et al. (1998) Aneurysm induced by periarterial application of elastase heals spontaneously. Int Angiol 17: 113–119.
[10]
White JV, Mazzacco SL (1996) Formation and growth of aortic aneurysms induced by adventitial elastolysis. Ann N Y Acad Sci 800: 97–120.
[11]
Miyake T, Aoki M, Nakashima H, Kawasaki T, Oishi M, et al. (2006) Prevention of abdominal aortic aneurysms by simultaneous inhibition of NFkappaB and ets using chimeric decoy oligonucleotides in a rabbit model. Gene Ther 13: 695–704.
[12]
Gertz SD, Kurgan A, Eisenberg D (1988) Aneurysm of the rabbit common carotid artery induced by periarterial application of calcium chloride in vivo. J Clin Invest 81: 649–656.
[13]
Freestone T, Turner RJ, Higman DJ, Lever MJ, Powell JT (1997) Influence of hypercholesterolemia and adventitial inflammation on the development of aortic aneurysm in rabbits. Arterioscler Thromb Vasc Biol 17: 10–17.
[14]
Isenburg JC, Simionescu DT, Starcher BC, Vyavahare NR (2007) Elastin stabilization for treatment of abdominal aortic aneurysms. Circulation 115: 1729–1737.
[15]
Tanaka A, Hasegawa T, Chen Z, Okita Y, Okada K (2009) A novel rat model of abdominal aortic aneurysm using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure. J Vasc Surg 50: 1423–1432.
[16]
Zhong H, Matsui O, Xu K, Ogi T, Okuda M, et al. (2009) Partially covered stent-graft implantation in rabbit aorta: a new model to investigate bioactive stent-grafts in small animals. J Endovasc Ther 16: 154–160.
[17]
Zhong H, Matsui O, Xu K, Ogi T, Sanada J, et al. (2009) Gene transduction into aortic wall using plasmid-loaded cationized gelatin hydrogel-coated polyester stent graft. J Vasc Surg 50: 1433–1443.
[18]
Fujiwara NH, Kallmes DF, Li ST, Lin HB, Hagspiel KD (2005) Type 1 collagen as an endovascular stent-graft material for small-diameter vessels: a biocompatibility study. J Vasc Interv Radiol 16: 1229–1236.
[19]
Cloft HJ, Kallmes DF, Lin HB, Li ST, Marx WF, et al. (2000) Bovine type I collagen as an endovascular stent-graft material: biocompatibility study in rabbits. Radiology 214: 557–562.
[20]
Kallmes DF, Fujiwara NH, Berr SS, Helm GA, Cloft HJ (2002) Elastase-induced saccular aneurysms in rabbits: a dose-escalation study. AJNR Am J Neuroradiol 23: 295–298.
[21]
Short JG, Fujiwara NH, Marx WF, Helm GA, Cloft HJ, et al. (2001) Elastase-induced saccular aneurysms in rabbits: comparison of geometric features with those of human aneurysms. AJNR Am J Neuroradiol 22: 1833–1837.
[22]
Anidjar S, Dobrin PB, Eichorst M, Graham GP, Chejfec G (1992) Correlation of inflammatory infiltrate with the enlargement of experimental aortic aneurysms. J Vasc Surg 16: 139–147.
[23]
Halpern VJ, Nackman GB, Gandhi RH, Irizarry E, Scholes JV, et al. (1994) The elastase infusion model of experimental aortic aneurysms: synchrony of induction of endogenous proteinases with matrix destruction and inflammatory cell response. J Vasc Surg 20: 51–60.
[24]
Palmieri D, Pane B, Barisione C, Spinella G, Garibaldi S, et al. (2011) Resveratrol Counteracts Systemic and Local Inflammation Involved in Early Abdominal Aortic Aneurysm Development. J Surg Res 171: e237–246.
[25]
Sinha I, Cho BS, Roelofs KJ, Stanley JC, Henke PK, et al. (2006) Female gender attenuates cytokine and chemokine expression and leukocyte recruitment in experimental rodent abdominal aortic aneurysms. Ann N Y Acad Sci 1085: 367–379.
[26]
Sinha I, Hannawa KK, Eliason JL, Ailawadi G, Deogracias MP, et al. (2004) Early MT-1 MMP expression following elastase exposure is associated with increased cleaved MMP-2 activity in experimental rodent aortic aneurysms. Surgery 136: 176–182.
[27]
Yamaguchi T, Yokokawa M, Suzuki M, Higashide S, Katoh Y, et al. (2001) Morphologic changes in the aorta during elastase infusion in the rat aneurysm model. J Surg Res 95: 161–166.
[28]
Zhang Q, Huang JH, Xia RP, Duan XH, Jiang YB, et al. (2011) Suppression of experimental abdominal aortic aneurysm in a rat model by the phosphodiesterase 3 inhibitor cilostazol. J Surg Res 167: e385–393.
[29]
Huang G, Wang A, Li X, Long M, Du Z, et al. (2009) Change in high-sensitive C-reactive protein during abdominal aortic aneurysm formation. J Hypertens 27: 1829–1837.
[30]
Kobayashi H, Matsushita M, Oda K, Nishikimi N, Sakurai T, et al. (2004) Effects of atherosclerotic plaque on the enlargement of an experimental model of abdominal aortic aneurysm in rabbits. Eur J Vasc Endovasc Surg 28: 71–78.
[31]
Matsushita M, Kobayashi H, Oda K, Nishikimi N, Sakurai T, et al. (1999) A rabbit model of abdominal aortic aneurysm associated with intimal thickening. Eur Surg Res 31: 305–313.
[32]
Basalyga DM, Simionescu DT, Xiong W, Baxter BT, Starcher BC, et al. (2004) Elastin degradation and calcification in an abdominal aorta injury model: role of matrix metalloproteinases. Circulation 110: 3480–3487.
[33]
Chiou AC, Chiu B, Pearce WH (2001) Murine aortic aneurysm produced by periarterial application of calcium chloride. J Surg Res 99: 371–376.
[34]
Longo GM, Xiong W, Greiner TC, Zhao Y, Fiotti N, et al. (2002) Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. J Clin Invest 110: 625–632.
[35]
Tsuruda T, Kato J, Hatakeyama K, Kojima K, Yano M, et al. (2008) Adventitial mast cells contribute to pathogenesis in the progression of abdominal aortic aneurysm. Circ Res 102: 1368–1377.
[36]
Mastoraki ST, Toumpoulis IK, Anagnostopoulos CE, Tiniakos D, Papalois A, et al. (2012) Treatment with simvastatin inhibits the formation of abdominal aortic aneurysms in rabbits. Ann Vasc Surg 26: 250–258.
[37]
Schulz H, Mohr M, Meyer M (1989) Elastase and papain inhibition by serum of mammals. Scand J Clin Lab Invest 49: 381–388.
[38]
Hoshina K, Nakahashi TK, Sho E, Sho M, Tsao P, et al. (2003) Aortic wall shear stress modulates aneurysm cellularity and structure. J Vasc Surg 37: 1067–1074.
[39]
Hanke H, Strohschneider T, Oberhoff M, Betz E, Karsch KR (1990) Time course of smooth muscle cell proliferation in the intima and media of arteries following experimental angioplasty. Circ Res 67: 651–659.
