Abdominal aortic aneurysms (AAAs) are manifested with progressive luminal dilatation and a high risk for aortic rupture. In the past 2 decades, mechanisms of this devastating disease have been explored using multiple mouse models. Since early 2000, three AAA mouse models have been commonly used: angiotensin II infusion,
1
periaortic application of CaCl2,2
and intraluminal perfusion of elastase.3
In 2012, Bhamidipati et al. modified the intraluminal perfusion of elastase model with an easier surgical procedure involving periadventitial application.4
However, as with the intraluminal elastase perfusion model, there was modest luminal dilatation and no aortic rupture. Recently, Lu et al. modified this mouse model to provoke more severe pathological manifestations:5
in addition to the periadventitial application of elastase, mice are administered β-aminopropionitrile (BAPN) in drinking water. Prolonged administration of BAPN leads to progressive luminal dilatation of the infrarenal aorta, thrombosis, and spontaneous infrarenal aortic rupture, which mimics several aspects of human AAAs.5
This model has become popular for studying the pathogenesis and mechanisms of AAAs.6
, 7
, 8
In this issue, Gueldner et al.
9
studied the mechanical and matrix effects using the periadventitial elastase mouse model with different durations of BAPN administration. The authors performed mechanical testing of fresh aortic sections to determine the tangent modulus (representing the stiffness of the aorta) and ultimate tensile strength (UTS; representing the maximal elasticity). Compared to the sham group, mice applied with elastase alone had increased tangent modulus but no change on UTS. These data support the notion that the infrarenal aortic damage by elastase application had increased wall stiffness, but had no change in wall strength two weeks after elastase application. Administration of BAPN for 4 or 14 days after elastase application did not change either tangent modulus or UTS, whereas administration of BAPN for 8 weeks reduced both tangent modulus and UTS. These data support that prolonged administration of BAPN led to progressive structural and functional impairment of the already damaged aortic wall by periaortic elastase application.Subsequently, the authors performed quantitative structural matrix protein analysis. Considering the complex pathology and intraluminal thrombus in mice administered BAPN for 8 weeks, this group was excluded for comparisons. Mice administered elastase alone had less insoluble elastin and low content of collagen. Administration of BAPN for either 4 or 14 days did not change elastin. Collagen was modestly higher in mice administered BAPN for 4 days, but not for 14 days. To understand why aortic aneurysms are more frequent in the infrarenal region, the authors compared the descending thoracic aorta and the infrarenal aorta in the sham group. The infrarenal aorta had lower tangent modulus and higher collagen content, but had no difference on UTS and elastin, compared to the descending thoracic aorta.
In conclusion, the study by Gueldner et al.
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determined temporal alterations of biomechanical properties and matrix profiles during AAA formation using the periadventitial elastase application with BAPN administration mouse model, which provides important insights into the pathological and mechanistic complexity of human AAAs.References
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- Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms.J Clin Invest. 2002; 110: 625-632
- Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms.J Clin Invest. 2000; 105: 1641-1649
- Development of a novel murine model of aortic aneurysms using peri-adventitial elastase.Surgery. 2012; 152: 238-246
- A novel chronic advanced stage abdominal aortic aneurysm murine model.J Vasc Surg. 2017; 66 (42.e4): 232
- High-frequency murine ultrasound provides enhanced metrics of BAPN-induced AAA growth.Am J Physiol Heart Circ Physiol. 2019; 317: H981-H990
- Biomechanical consequences of compromised elastic fiber integrity and matrix cross-linking on abdominal aortic aneurysmal enlargement.Acta Biomater. 2021; 134: 422-434
- Translating mouse models of abdominal aortic aneurysm to the translational needs of vascular surgery.JVS Vasc Sci. 2021; 2: 219-234
- Mechanical and matrix effects of short and long-duration exposure to BAPN in elastase-induced model AAA in mice.JVascSurg. 2023; (In Press)
Article info
Publication history
Accepted:
January 20,
2023
Received:
January 16,
2023
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Funding
The authors’ research work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL139748 and R35HL155649) and the American Heart Association SFRN in Vascular Disease (18SFRN33960163). The content in this editorial is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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- Mechanical and matrix effects of short and long-duration exposure to BAPN in elastase-induced model AAA in mice.JVS-Vascular ScienceOpen Access
