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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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Synergistic elastase and papain injury drives abdominal aortic aneurysm formation and rupture in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月3日

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  • Santiago Elizondo-Benedetto,
  • Mohamed S. Zaghloul,
  • Batool Arif,
  • Ibrahim Kuziez,
  • Ryan Wahidi,
  • Mohamed A. Zayed

摘要

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.