Research Article: Rabbit aortic aneurysm model with enlarging diameter capable of better mimicking human aortic aneurysm disease

Date Published: June 11, 2018

Publisher: Public Library of Science

Author(s): Yonghua Bi, Hongmei Chen, Yahua Li, Zepeng Yu, Xinwei Han, Jianzhuang Ren, Michael Bader.

http://doi.org/10.1371/journal.pone.0198818

Abstract

The self-healing phenomenon can be found in the elastase-induced abdominal aortic aneurysm (AAA) model, and an enlarging AAA model was successfully induced by coarctation. Unfortunately, aortic coarctation in these enlarging models is generally not found in human AAA disease. This study aimed to create an experiment model of enlarging AAA in rabbits to better mimic human aortic aneurysm disease. Eighty-four male New Zealand white rabbits were randomly divided into three equal groups: two aneurysm groups (A and B) and a SHAM group. Aneurysm group rabbits underwent extrinsic aortic stenosis below the right renal artery and received a 10-minute incubation of 60 μl elastase (1 unit/μl). Absorbable suture was used in Group A and nonabsorbable cotton thread was used in Group B. A sham operation was performed in the SHAM group. Aortic diameter was measured after 1, 3, 7, and 15 weeks; thereafter animals were sacrificed for histopathological, immunohistochemical and quantitative studies. Two rabbits died at 29 and 48 days, respectively, after operation in Group B. All aneurysms formed and enlarged progressively by 3 weeks in the Aneurysm groups. However, diameter enlargement in Group A was significantly lower than that in Group B at 7 weeks. Aneurysm groups developed intimal hyperplasia; intima-media thickness (IMT) increased significantly by week 7, and aortic media thickness and intima-media ratio (IMR) increased significantly by week 15. Marked destruction of elastin fibers and smooth muscle cells (SMCs) occurred 1 week later and increased progressively thereafter. Intimal hyperplasia and SMCs content in Group A increased significantly by week 15 compared with Group B. Aneurysm groups exhibited strong expression of matrix metalloproteinases 2 and 9 and RAM11 by week 1, and decreased progressively thereafter. In conclusion, this novel rabbit AAA model enlarges progressively without coarctation and is capable of better mimicking human aortic aneurysm disease.

Partial Text

Abdominal aortic aneurysm (AAA), a life-threatening disease, is characterized by chronic inflammation and remodeling of aortic wall tissue [1]. However, the pathogenesis of AAA remains poorly understood [2]. Experimental AAA models have been developed in small animals to mimic human AAA disease. The small animal models have been classified into three categories: chemical injury aneurysm model, genetically predisposed animal model, and hemodynamically-induced aneurysm model [3]. Chemical injury aneurysms induced by elastase and calcium chloride are popular models [4–13]. However, elastase and calcium chloride does not always induce AAA formation [14–16]. It has been reported that aneurysm diameter increases no more than 70% [5,7,8] and even heals spontaneously in elastase-induced AAA models [7]. Human AAA will enlarge progressively and cause aneurysm rupture or even death [17]. A new kind of enlarging AAA model was successfully induced in rats [18] and rabbits [19] to successfully overcome the self-healing phenomenon reported by Origuchi et al. [7]. Unfortunately, aortic coarctation in these enlarging models is generally not found in human AAA disease, which also poses difficulty for further interventional procedures, such as stent implantation. In this study, we modified this method and induced rabbit AAA model with enlarging diameter to better mimic human aortic aneurysm disease.

All aneurysms formed 3 weeks after a combination of elastase incubation and absorbable suture caused stenosis. The suture absorbed about 4 weeks later to terminate the aortic coarctation, and rabbit AAA model remained stable thereafter. The diameter increased to 6.2 ± 0.6 mm by the end of follow up (15 weeks) and was significant higher than that of the elastase-induced model. This novel AAA model showed typical hisopathological/immunohistochemical changes, MMP expression, and inflammatory infiltration. Elastin fibers and SMCs were destroyed markedly, with strong expression of matrix metalloproteinase 2, 9 and RAM11 1 week later. However, intimal hyperplasia, elastin fibers and SMCs content increased progressively thereafter. These complex changes are quite helpful for further investigation of the pathogenesis of AAA formation and progression.

 

Source:

http://doi.org/10.1371/journal.pone.0198818

 

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