Novel Papain-Elastase Induced Murine Model for Infrarenal Abdominal Aortic Aneurysm Rupture

Abdominal aortic aneurysm (AAA) rupture leads to high morbidity and mortality. Current rodent models struggle to reliably mimic infrarenal AAA rupture. Chemical treatments using porcine pancreatic elastase (PPE), papain (Pap), β-aminopropionitrile (BAPN), and angiotensin II (ANG II) are known to induce AAA in rodents. We hypothesized that combining these agents could establish reliable chronic AAA and acute rupture models, resembling human pathology. Here AAAs were induced in male C57BL/6 mice using peri-adventitial exposure to PPE, Pap, or a combination (PPE + Pap), with or without 0.3% BAPN and ANG II. Two weeks post-induction, Pap and PPE + Pap showed increased aortic diameters, higher inflammation, elastase degradation, and matrix metallopeptidase (MMP) activity. Addition of BAPN resulted in large chronic AAAs (500% growth) and intraluminal thrombus (ILT) formation. ANG II-treated mice exhibited a 93% rupture rate, increased inflammation, MMP activation, and ILT formation. These novel murine models are ideal for investigating AAA pathophysiology and therapeutic discovery.