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Elastase is not sufficient to induce experimental abdominal aortic aneurysms.
C G Carsten1, W C Calton, J M Johanning
1Section of Vascular Surgery and Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, Pa 17822-2150, USA.
Journal of Vascular Surgery
|June 5, 2001
Summary
Variability in elastase preparations affects abdominal aortic aneurysm (AAA) rat models. Inflammatory modifiers, not elastolytic activity, are key to AAA induction, necessitating lot-specific controls.
Area of Science:
- Vascular Biology
- Biomedical Research Models
Background:
- Abdominal aortic aneurysms (AAAs) are often studied using a rat model.
- This model typically involves inducing AAAs via aortic infusion of porcine pancreatic elastase.
- Significant variability in AAA size across studies suggests issues with elastase preparations.
Purpose of the Study:
- To investigate lot-to-lot variations in elastase preparations.
- To identify factors contributing to variability in AAA induction in the rat model.
- To understand the relationship between elastase purity, inflammation, and AAA formation.
Main Methods:
- Evaluated four lots of porcine pancreatic elastase in the standard rat AAA model.
- Administered varying concentrations of elastase, with and without thioglycollate medium (macrophage activator).
- Assessed aortic diameters, histological inflammation, elastin degradation, and elastase activity/purity.
Main Results:
- Only one of four elastase lots consistently induced AAAs at standard doses.
- Higher elastase concentrations and thioglycollate medium improved AAA induction in some lots.
- High-purity elastase failed to induce AAAs; AAA size correlated with inflammation, not elastin degradation.
Conclusions:
- Elastolytic activity alone does not guarantee AAA formation.
- Inflammatory modifiers in elastase preparations, rather than purity, appear crucial for AAA induction.
- Future AAA rat model studies require careful consideration of elastase lot variability and controls.