Advanced Abdominal Aortic Aneurysm Modeling in Mice by Combination of Topical Elastase and Oral ß-aminopropionitrile
July 26th, 2024
This protocol describes a methodical surgical approach to modeling advanced abdominal aortic aneurysms in mice by a combination of directly applying elastase to the infrarenal aorta and administering ß-aminopropionitrile through drinking water.
Our research aims to understand the pathophysiology of abdominal aortic aneurysm. In particular, we like to know in the molecular term how aneurysm ruptures. We believe by modeling aortic aneurysm in mice, males and females, will help us to develop a new treatment for this highly lethal disease that urgently needs pharmacological treatment.
The pathophysiology of abdominal aortic aneurysm is multifactorial and complex, which makes animal modeling difficult. The elastase/BAPN model, however, reliably produces aneurysms in mice, which model many of the features and characteristics of the human disease. Combining BAPN drinking water with topical elastase surgery can produce large true infrarenal aneurysms, which form intraluminal thrombus, progressively dilate, and eventually rupture.
This allows researchers the opportunity to study features like rupture risk and aneurysm growth.
Overview
This research aims to elucidate the pathophysiology of abdominal aortic aneurysm (AAA) through a reliable mouse model. By employing a combination of elastase application and administration of ß-aminopropionitrile (BAPN), the study successfully replicates features of the human disease, enabling insights into aneurysm growth and rupture.
Key Study Components
Research Area
- Pathophysiology of abdominal aortic aneurysm
- Animal modeling of complex diseases
- Pharmacological treatment development
Background
- AAA is a multifactorial condition with high mortality rates.
- The elastase/BAPN model is an effective method to study AAA in mice.
- Understanding rupture mechanisms can inform treatment strategies.
Methods Used
- Animal models using mice
- Topical elastase application combined with BAPN in drinking water
- Monitoring aneurysm growth and rupture risk
Main Results
- Successful formation of large true infrarenal aneurysms in mice.
- Intravascular thrombus formation and progressive dilation observed.
- Demonstrated reliable modeling of human AAA features.
Conclusions
- The study validates an effective method for AAA research in mice.
- Findings can advance the development of new therapeutic options for AAA.
Frequently Asked Questions
Executive Industry Relevance
Reliable modeling of abdominal aortic aneurysm (AAA) in mice using combined topical elastase and oral BAPN enables mechanistic de-risking and target validation for vascular disease research. This approach recapitulates key features of human AAA, supporting predictive confidence in preclinical studies and informing risk-adjusted portfolio decisions for therapeutic development.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables interrogation of molecular mechanisms underlying aneurysm growth and rupture.
- Supports functional target validation by modeling human-like AAA pathology in vivo.
- Facilitates biological de-risking for candidate targets implicated in vascular remodeling.
Screening & Assay Development
- Provides a standardized, reproducible in vivo system for evaluating pharmacological interventions.
- Enables quantitative assessment of aneurysm progression and rupture endpoints.
- Supports assay readiness for compound screening targeting AAA pathophysiology.
Translational & Preclinical Research
- Aligns preclinical model features with human disease, enhancing translational relevance.
- Enables study of rupture risk and biomarker development for AAA progression.
- Supports continuity from discovery through preclinical validation of vascular therapeutics.
Pipeline & Workflow Integration
This refined murine AAA model integrates into the discovery-to-preclinical continuum, bridging early mechanistic studies with translational research on aneurysm growth and rupture.
- Discovery Biology: Facilitates hypothesis testing on molecular drivers of aneurysm formation and rupture.
- Screening: Provides a reproducible platform for evaluating intervention efficacy and safety in vivo.
- Analytics: Enables quantitative measurement of aneurysm size, thrombus formation, and rupture incidence.
- Translational Research: Enhances alignment with human AAA features for biomarker and therapeutic validation.
- Enterprise Reuse: Offers a standardized model adaptable across research teams and therapeutic programs.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence and reduces mechanistic ambiguity in AAA research.
- Operational Value: Improves reproducibility and standardization of in vivo vascular modeling.
- Strategic Value: Informs go/no-go decisions and prioritizes candidates with validated mechanistic impact.
- Portfolio Impact: Supports risk-adjusted advancement of vascular disease programs.
Implementation Considerations
- Requires expertise in murine vascular surgery and animal model management.
- Needs access to surgical instrumentation and quantitative imaging for aneurysm assessment.
- Demands cross-team standardization of surgical and analytical protocols.
- Adaptable to both male and female mice for broader translational relevance.
- Dependent on consistent BAPN administration and elastase application for reproducibility.
