The synergistic combination of pancreatic elastase, papain, BAPN, and angiotensin II induced a 93% abdominal aortic aneurysm rupture rate in mice, significantly higher than individual treatments.
Does a combination of pancreatic elastase, papain, BAPN, and ANG II induce abdominal aortic aneurysm formation and rupture in mice?
A synergistic combination of pancreatic elastase, papain, BAPN, and ANG II creates a robust murine model that closely replicates human abdominal aortic aneurysm formation and rupture.
Absolute Event Rate: 93% vs 0%
p-value: p=0.003
Abstract Background Abdominal aortic aneurysm (AAA) rupture leads to high morbidity and mortality. Current rodent models struggle to reliably mimic infrarenal AAA rupture. Chemical treatments using pancreatic elastase (PE), papain (Pa), β-aminopropionitrile (BAPN), and angiotensin II (ANG II) are known to induce AAA in rodents. We hypothesized that combining these agents can synergistically lead to acute AAA rupture models, as well as chronic AAA models that closely resemble human pathology. Methods AAAs were induced in 125 male C57BL/6 mice via peri-adventitial exposure for twenty minutes using a cotton ball with either PE, Pa, or a combination of both (PE+Pa), with or without BAPN and ANG II. Results Two weeks post-induction, all groups exhibit significantly elevated aortic diameters, increased inflammation, elastin and collagen degradation, and matrix metallopeptidase (MMP) activity. The addition of BAPN results in large chronic AAAs (500% growth) and intraluminal thrombus (ILT) formation. Further addition of ANG II results in a 93% rupture rate in the PE+Pa group, significantly increased compared to PE and Pa alone. Compared to previous models, the PE+Pa, BAPN and ANG II combination demonstrates an increase in rupture events, inflammation, and MMP activation. Conclusions This murine model, using a synergistic combination of pancreatic elastase and papain, effectively replicates AAA pathophysiology and is ideal for investigating underlying mechanisms and potential therapeutic interventions.
Elizondo-Benedetto et al. (Tue,) conducted a other in Abdominal aortic aneurysm (n=125). Pancreatic elastase and papain (PE+Pa) with BAPN and ANG II vs. 5'PE (pancreatic elastase alone for 5 minutes) was evaluated on AAA rupture rate (p=0.003). The synergistic combination of pancreatic elastase, papain, BAPN, and angiotensin II induced a 93% abdominal aortic aneurysm rupture rate in mice, significantly higher than individual treatments.