Abstract 102: Model-Dependent Influence of Prior Splenectomy on Experimental Abdominal Aortic Aneurysm Progression

Abstract

Objective: Abdominal aortic aneurysm (AAA) is a macrophage-driven, inflammatory vascular disease. Thus, mobilization of macrophage precursors from the bone marrow and/or splenic reservoir may represent a crucial initial step for AAA formation. Prior evidence suggests that splenic monocytes are important initial contributors to ischemic myocardial injury, their role in AAA pathogenesis remains unknown. We surgically removed the spleen prior to AAA creation to evaluate the influence of splenic monocytes on aneurysm pathophysiology. Methods: AAAs were created in either 1) male C57BL/6 mice by infrarenal intra-aortic porcine pancreatic elastase (PPE) infusion or 2) male ApoE deficient mice by continuous subdermal angiotensin II infusion (ApoE KO/Ang II model). Splenectomy was performed immediately prior to AAA creation in both models. Aortic diameter was serially monitored via ultrasonography, and aortae harvested at sacrifice for histopathology. Results: In sham splenectomy mice, PPE infusion led to significant aortic enlargement. AAA (≥50% aortic diameter increase) developed in all sham/PPE mice within 14 days (n=10). Splenectomy effectively eliminated PPE-induced aortic enlargement, with preservation of medial elastin and smooth muscle cell density and minimal inflammation compared to sham. In contrast, Ang II infusion in ApoE deficient produced similar-sized or larger AAA in splenectomized mice compared to sham, with elastin degradation, smooth muscle cell depletion undistinguishable between the groups. Conclusion: Splenectomy confers differential protection from AAA in mice, depending on the model/method employed for aneurysm formation. While this experiment underscores important limitations to mouse-based AAA modeling, the splenic monocyte reservoir may represent an important driver of AAA pathophysiology.