Abstract 478: Altered Blood Flow and Anatomic Variations Increase the Translational Value of the PPE Murine Aneurysm Model

Abstract

Introduction: Abdominal aortic aneurysm (AAA) is an individual and socioeconomic burden in the aging society. Treatment relies on surgical exclusion of the dilated aorta by open or endovascular repair only. For research purposes, animal models are necessary and the elastase induced aneurysm model (PPE) has gained much attention for it closely mimics endstage human aneurysm disease. However, to improve the translational value of this model we conducted a couple of modifications in relation to human aneurysm morphology. Materials and Methods: In 10-week-old male C57BL/6J wild-type mice the classic PPE procedure with local perfusion of porcine pancreatic elastase in order to induce aneurysm was modified using flow alteration by partial ligation of the iliac artery or the aorta. Additionally, careful exploration of the abdominal aortic branches allowed PPE induction at the suprarenal and iliac level. Molecular biology, ultrasound and immunistochemistry were used to evaluate the results. Results: Aortic blood flow restriction (PPE 2.0) significantly increases murine AAA diameter and affects the localization of vascular wall remodeling. Suprarenal aortic dissection allows inducing a more proximal aneurysm (PPE 3.0) similar to the angiotensin II induced aneurysm model. Separate investigation for canonical activation of transforming growth factor ß in these two embryologically distinct segments shows no difference. Creating an aorto-iliac bifurcated aneurysm (PPE 4.0) completes the mimicry of human aneurysm morphologies. Conclusion: PPE is the most important model for AAA research and the ß-versions PPE 2.0, 3.0 and 4.0 modifying its morphology further increase the translational value.