An improved porcine model of infrarenal abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) remains a significant public health challenge, primarily due to its high mortality rate and the lack of effective preventive and causal strategies. This study aims to establish an improved translational triple-hit porcine model of AAA and to compare it with human AAA disease. AAA was induced in four juvenile domestic pigs by balloon catheter-based aortic dilation, enzyme-mediated extracellular matrix (ECM) degradation, and lysyl oxidase inhibition. The porcine AAA model was characterized by proteomics, histological investigation, and cytokine profiling, and compared with natural occurred human AAA disease. Infrarenal AAA was successfully established with sustained aortic dilation (> 150% of baseline diameter) occurring within 7-14 days post induction and maintained through day 28. Proteomic analysis of porcine AAA tissue identified significant shifts in protein abundance, including downregulation of proteins associated with vascular smooth muscle cell function and ECM integrity, and upregulation of immune-related proteins. Comparative analysis of porcine and human aortic tissues revealed reduced medial elastic fiber content and length, along with increased calcification in porcine AAA, reflecting structural and pathological changes observed in human AAA. Systemic cytokine profiling revealed significant increases in both pro-inflammatory and anti-inflammatory cytokines following AAA induction in pigs, with a cytokine profile largely comparable to that observed in human AAA patients. These findings suggest that the refined porcine AAA model offers a reliable and reproducible platform for investigating AAA progression and evaluating potential therapeutic interventions prior to clinical implementation.