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Updated: May 2, 2026
A New Murine Model of Endovascular Aortic Aneurysm Repair
Published on: July 7, 2013
Rapamycin limits the growth of established experimental abdominal aortic aneurysms
1Division of Vascular Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Objectives:
Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease affecting 4-8% of men older than 60 years. No pharmacologic strategies limit disease progression, aneurysm rupture, or aneurysm-related death. We examined the ability of rapamycin to limit the progression of established experimental AAAs.
Methods:
AAAs were created in 10-12-week-old male C57BL/6J mice via the porcine pancreatic elastase (PPE) infusion method. Beginning 4 days after PPE infusion, mice were treated with rapamycin (5 mg/kg/day) or an equal volume of vehicle for 10 days. AAA progression was monitored by serial ultrasound examination. Aortae were harvested for histological analyses at sacrifice.
Results:
Three days after PPE infusion, prior to vehicle or rapamycin treatment, aneurysms were enlarging at an equal rate between groups. In the rapamycin group, treatment reduced aortic enlargement by 38%, and 53% at 3 and 10 days, respectively. On histological analysis, medial elastin and smooth muscle cell populations were relatively preserved in the rapamycin group. Rapamycin treatment also reduced mural macrophage density and neoangiogenesis.
Conclusion:
Rapamycin limits the progression of established experimental aneurysms, increasing the translational potential of mechanistic target of rapamycin-related AAA inhibition strategies.
Insights
Rapamycin effectively limits abdominal aortic aneurysm (AAA) progression in established experimental models. This study shows rapamycin preserves aortic structure and reduces inflammation, offering potential therapeutic strategies for AAA.
Area of Science:
- Vascular Biology
- Pharmacology
- Immunology
Background:
- Abdominal aortic aneurysm (AAA) is a prevalent inflammatory vascular disease in older men.
- Current treatments for AAA lack pharmacologic strategies to halt disease progression or prevent rupture.
- Established experimental AAAs provide a model to test therapeutic interventions.
Purpose of the Study:
- To investigate the efficacy of rapamycin in limiting the progression of established experimental abdominal aortic aneurysms (AAAs).
- To assess the impact of rapamycin on AAA size, aortic structure, and inflammatory markers.
Main Methods:
- Experimental AAAs were induced in mice using porcine pancreatic elastase (PPE).
- Mice with established AAAs received rapamycin or vehicle treatment for 10 days.
- AAA progression was monitored via ultrasound, and aortae were analyzed histologically.
Main Results:
- Rapamycin treatment significantly reduced aortic enlargement by 38% and 53% at 3 and 10 days, respectively.
- Histological analysis revealed preserved medial elastin and smooth muscle cells in rapamycin-treated aortae.
- Rapamycin reduced mural macrophage density and neoangiogenesis within the aneurysm wall.
Conclusions:
- Rapamycin demonstrates a significant inhibitory effect on the progression of established experimental AAAs.
- These findings support the translational potential of mechanistic target of rapamycin (mTOR)-related strategies for AAA treatment.
- Rapamycin may offer a novel pharmacologic approach to manage AAA disease progression and reduce rupture risk.
