Abstract 1010: Novel Murine Model For Infrarenal Abdominal Aortic Aneurysm Development And Rupture

Abstract

Introduction: Abdominal Aortic Aneurysm (AAA) rupture is linked with increased mortality. Multiple rodent models attempt to capitulate AAA pathology to investigate a preventative cure. However, there are currently no murine models that reliably mimic AAA rupture. Compounds such as porcine pancreatic elastase (PPE), papain, β-aminopropionitrile (BAPN) and angiotensin II (ANG II) can independently promote AAA formation in rodents. We hypothesize that combining these agents can lead to reliable infrarenal AAA rupture model in mice. Methods: 28 male C57BL/6 mice underwent aortic topical exposure to 50μL of either saline (sham), PPE, papain or both PPE+papain (20 & 10.3mg/mL respectively) for 20 minutes with a cotton ball to induce AAA degeneration. A group of 10 mice were also exposed to BAPN at 0.3% via drinking water (Fig 1A). After 3 days, another group of 5 mice was further exposed to ANG II subcutaneous pump. Weight and in vivo aortic size were measured longitudinally. Mice that died spontaneously were promptly assessed to evaluate for AAA rupture (Fig 1B). All remaining mice were sacrificed at week 4. Results: Compared to sham, mice exposed to papain or PPE+papain, but no BAPN or ANG II, demonstrated no change in weight gain, but significantly increased aortic diameter at week 4 (p<0.01) while administration of 0.3% BAPN demonstrated further increase in AAA diameter in both groups (p=0.002 and p<0.001, respectively; Fig 1C). All mice that received PPE+papain+0.3% BAPN as well as ANG II pump developed infrarenal AAAs and 80% developed a free rupture by day 9 (Fig 1D). Conclusion: We present a novel murine model that provides a high rate of infrarenal AAA development and rupture. The model not only combines matrix degradation, but also impulse risk factors known to enhance AAA rupture in humans. The feasibility and reliability of the model facilitates its use in future murine genetic and pharmacological studies that aim to understand AAA pathophysiology and methods of prevention.