Development of a Novel Rabbit Model of Abdominal Aortic Aneurysm Via a Combination of Periaortic Calcium Chloride and Elastase Incubation

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Jul 12

PMID 23844207

Citations 10

Authors

Yonghua Bi

Hongshan Zhong

Ke Xu

Zhen Zhang

Xun Qi

Yonghui Xia

Ling Ren

Affiliations

Soon will be listed here.

Abstract

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.

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References

Matsushita M, Kobayashi H, Oda K, Nishikimi N, Sakurai T, Nimura Y . A rabbit model of abdominal aortic aneurysm associated with intimal thickening. Eur Surg Res. 1999; 31(4):305-13. DOI: 10.1159/000008707. View

Freestone T, Turner R, Higman D, Lever M, Powell J . Influence of hypercholesterolemia and adventitial inflammation on the development of aortic aneurysm in rabbits. Arterioscler Thromb Vasc Biol. 1997; 17(1):10-7. DOI: 10.1161/01.atv.17.1.10. View

Zhong H, Matsui O, Xu K, Ogi T, Okuda M, Liu Y . Partially covered stent-graft implantation in rabbit aorta: a new model to investigate bioactive stent-grafts in small animals. J Endovasc Ther. 2009; 16(2):154-60. DOI: 10.1583/08-2617.1. View

Ernst C . Abdominal aortic aneurysm. N Engl J Med. 1993; 328(16):1167-72. DOI: 10.1056/NEJM199304223281607. View

Tsuruda T, Kato J, Hatakeyama K, Kojima K, Yano M, Yano Y . Adventitial mast cells contribute to pathogenesis in the progression of abdominal aortic aneurysm. Circ Res. 2008; 102(11):1368-77. DOI: 10.1161/CIRCRESAHA.108.173682. View

Shimizu K, Mitchell R, Libby P . Inflammation and cellular immune responses in abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 2006; 26(5):987-94. DOI: 10.1161/01.ATV.0000214999.12921.4f. View

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(2):113-9. View

Anidjar S, Dobrin P, Eichorst M, GRAHAM G, Chejfec G . Correlation of inflammatory infiltrate with the enlargement of experimental aortic aneurysms. J Vasc Surg. 1992; 16(2):139-47. DOI: 10.1067/mva.1992.35585. View

Sinha I, Cho B, Roelofs K, Stanley J, Henke P, Upchurch Jr G . Female gender attenuates cytokine and chemokine expression and leukocyte recruitment in experimental rodent abdominal aortic aneurysms. Ann N Y Acad Sci. 2006; 1085:367-79. DOI: 10.1196/annals.1383.027. View

10.

Gertz S, 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(3):649-56. PMC: 442510. DOI: 10.1172/JCI113368. View

11.

Halpern V, Nackman G, Gandhi R, Irizarry E, Scholes J, Ramey W . 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(1):51-60. DOI: 10.1016/0741-5214(94)90175-9. View

12.

Jiao L, Xu Z, Xu F, Zhang S, Wu K . Vascular smooth muscle cell remodelling in elastase-induced aortic aneurysm. Acta Cardiol. 2010; 65(5):499-506. DOI: 10.1080/ac.65.5.2056235. View

13.

Yamaguchi T, Yokokawa M, Suzuki M, Higashide S, Katoh Y, Sugiyama S . Morphologic changes in the aorta during elastase infusion in the rat aneurysm model. J Surg Res. 2001; 95(2):161-6. DOI: 10.1006/jsre.2000.6025. View

14.

Schulz H, Mohr M, Meyer M . Elastase and papain inhibition by serum of mammals. Scand J Clin Lab Invest. 1989; 49(4):381-8. DOI: 10.3109/00365518909089111. View

15.

Sinha I, Hannawa K, Eliason J, Ailawadi G, Deogracias M, Bethi S . Early MT-1 MMP expression following elastase exposure is associated with increased cleaved MMP-2 activity in experimental rodent aortic aneurysms. Surgery. 2004; 136(2):176-82. DOI: 10.1016/j.surg.2004.04.010. View

16.

Chiou A, Chiu B, Pearce W . Murine aortic aneurysm produced by periarterial application of calcium chloride. J Surg Res. 2001; 99(2):371-6. DOI: 10.1006/jsre.2001.6207. View

17.

Anidjar S, Salzmann J, Gentric D, LAGNEAU P, Camilleri J, Michel J . Elastase-induced experimental aneurysms in rats. Circulation. 1990; 82(3):973-81. DOI: 10.1161/01.cir.82.3.973. View

18.

Sasaki K, Ujiie H, Higa T, Hori T, Shinya N, Uchida T . Rabbit aneurysm model mediated by the application of elastase. Neurol Med Chir (Tokyo). 2004; 44(9):467-73, discussion 473-4. DOI: 10.2176/nmc.44.467. View

19.

Isenburg J, Simionescu D, Starcher B, Vyavahare N . Elastin stabilization for treatment of abdominal aortic aneurysms. Circulation. 2007; 115(13):1729-37. DOI: 10.1161/CIRCULATIONAHA.106.672873. View

20.

Hoshina K, Sho E, Sho M, Nakahashi T, Dalman R . Wall shear stress and strain modulate experimental aneurysm cellularity. J Vasc Surg. 2003; 37(5):1067-74. DOI: 10.1016/s0741-5214(03)70052-4. View