A novel swine model of abdominal aortic aneurysm

Abstract

Objective: Few large animal models exist for the study of aortic aneurysms. βaminopropionitrile (BAPN) is a compound known to cause aortic aneurysms by inhibiting lysyl oxidase, a collagen cross-linking enzyme. It is hypothesized that BAPN plus aneurysm induction surgery would result in significant aneurysm formation in swine with biologic properties similar to human disease. Methods: Initial experiments were performed in uncastrated male swine not treated with BAPN (surgery alone). Subsequently, uncastrated male swine were fed BAPN (0.15 grams/kilogram) for 7 days before undergoing surgery: the infrarenal aorta was circumferentially dissected and measured, balloon dilated, perfused with elastase (500 units) and Type 1 collagenase (8000 units), with extraluminal elastase application. In the BAPN groups, daily BAPN feedings continued until swine harvest at postoperative days 7, 14, and 28. Results: Swine undergoing surgery alone (n=12) had significantly less dilation at 28 days compared with BAPN + surgery swine (51.9±29.2% (0-100%) vs. 113.5±30.2% (52.9-146.2%); p<0.0003). Mean aortic dilation in animals undergoing treatment with surgery and BAPN was 86.9%±47.4% (range, 55.6-157.1%), 105.4%±58.1% (50-133.3%), and 113.5%±30.2% (52.9-146.2%) at 7, 14, and 28 days, respectively. In the BAPN + surgery group, significant elastolysis was present at all time points, while aortic wall collagen content was not significantly different. Smooth muscle cells were significantly depleted at 14 and 28 days, and M1 macrophages were increased at 14 and 28 days (p<0.05, all). Matrix metalloproteinase 2 was elevated at 7 days

Maresin 1 activates LGR6 signaling to inhibit smooth muscle cell activation and attenuate murine abdominal aortic aneurysm formation

“…The synergistic effect of RvD1 on the aortic inflammation and MaR1 on apoptotic SMC uptake underscores the multifaceted approach of combined therapeutic intervention by bioactive isoforms of SPMs that will be deciphered in our recently described large animal porcine model as well as chronic aortic aneurysm and aortic rupture models. 25,45,47 In conclusion, treatment with MaR1 can significantly prevent, as well as slow the growth of small pre-formed AAAs in a murine model. The mechanistic approach of MaR1-mediated F I G U R E 7 Schematic description of MaR1-mediated attenuation of vascular remodeling during AAA formation.…”

Single-Photon Emission Computed Tomography Imaging Using Formyl Peptide Receptor 1 Ligand Can Diagnose Aortic Aneurysms in a Mouse Model

“…18,40,41 Further studies in large animals that is our recently described swine model of AAA as well as murine aortic rupture model, will enhance and validate clinical translatability of the c-FLFLFebased SPECT imaging for diagnosing and monitoring the progression of AAA. [42][43][44] In addition, as mentioned previously, SPECT does not provide the same spatiotemporal resolution as MRI or PET scans. However, an advantage of cFLFLF probe is that it can be coupled with radioisotopes specific for PET, such as Cu-64, 14 and future studies can decipher these additional imaging modalities for diagnosing AAA.…”

Aneurysms and dissections - What is new in the literature of 2019/2020 - a European Society of Vascular Medicine annual review

“…Shannon et al created a reproducible, clinically significant infrarenal AAA model in swine. To achieve this, Cullen et al used a combination of balloon angioplasty, elastase and collagenase, and a lysyl oxidase inhibitor, called β-aminopropionitrile (BAPN), to create clinically significant infrarenal AAs, analogous to human disease [29].…”