A novel chronic advanced stage abdominal aortic aneurysm murine model

Area of Science:

• Vascular Biology
• Surgical Models
• Biomedical Research

Background:

• Abdominal aortic aneurysm (AAA) poses significant health risks.
• Developing reliable animal models is crucial for understanding AAA pathogenesis.
• Existing models may not fully recapitulate chronic, advanced AAA features.

Purpose of the Study:

• To establish a reproducible and chronic mouse model of abdominal aortic aneurysm (AAA).
• To characterize the AAA development and progression using a combined BAPN and elastase approach.
• To provide a valuable tool for investigating late-stage AAA pathology and therapeutic interventions.

Main Methods:

• Utilized 8-week-old male C57BL/6 mice, divided into three groups: BAPN, elastase, and BAPN+elastase.
• Administered 0.2% BAPN in drinking water and/or applied active elastase to the infrarenal aorta.
• Collected aortic samples at multiple time points (7-100 days) for diameter measurement, histology, cytokine analysis, and zymography.

Main Results:

• The BAPN+elastase group showed a significantly higher AAA formation rate (93%) and more advanced stages compared to the elastase group (65%).
• Aneurysms in the BAPN+elastase group exhibited sustained growth, thrombus formation (54%), and rupture (31%).
• Elevated pro-inflammatory cytokines and MMP activity were observed early, with persistent MMP2 activity and increased T-cells later in the BAPN+elastase group.

Conclusions:

• Combined BAPN and elastase administration effectively induces a chronic, advanced AAA model in mice.
• This model mimics key AAA characteristics including persistent growth, thrombus, and rupture.
• The established model is suitable for future research on tissue remodeling in late-stage AAA development.