Rodent Models of Abdominal Aortic Aneurysm: How Far are Mice Men?

Abstract

Introduction: Rodent models of abdominal aortic aneurysm (AAA) are most commonly employed to investigate mechanisms important in aneurysm development and progression. These models have reported successful medical aneurysm stabilization. Unfortunatetly, these results failed to be transferred to human AAAs. This paradoxon stimulated us to investigate the gene expression profile from aortic tissue of two rodent models and compare it to the profile from human AAA wall samples. The aim of this study was to gain a deeper insight on the strengths and weaknesses of each model. Methods: We compared the gene expression profiles of the elastase (PPE; 1 week n=5 vs. 5 saline infused) and AngII ApoE-/-(AngII; n=5 vs. 6 saline controls) model with the human AAA expression profile (n=48 vs. 10 donors). The intersection of differentially expressed genes (|log2FC| ≥1.5, adjusted P< 0.05) in all analysis was identified. Canonical pathways were analyzed using Ingenuity Pathway Analysis (IPA) considering transcripts with an absolute log2FC ≥1 as differentially expressed. Results: Our study reflected a poor interspecies correlation when comparing individual transcripts (99 up- and 119 downregulated for PPE, 79 up- and 100 downregulated for AngII). But, IPA revealed a strong reflection of activated inflammatory pathways in both models. While the PPE model showed similarities to activated pathways related to innate immunity and cell organization/trafficing, the AngII model shares the inactivation of metabolic pathways with the human AAA. Conclusion: Despite their common application as representative models of AAA, their relevance for human AAA disease has been unclear. Our results show that the PPE model is dominated by inflammation and immunity and therefore is an initiation model. Even though the AngII model is often considered a dissection model, it results in similar end stage as human AAA, which is dominated by metabolic changes. These findings will help to adequately employ these models in further investigations on AAA development and progression. Disclosure: Nothing to disclose