Reliable Creation of a Murine Abdominal Aortic Aneurysm Model Using Elastin Sensitization and Perivascular Elastase

Degradation of the elastic lamellar matrix in the abdominal aortic wall is a histopathologic feature of abdominal aortic aneurysms (AAA). Growing evidence implicates elastin degradation and related host immune responses in the pathogenesis of AAA. Effective modeling of these processes is important for improving the understanding and treatment of this common disease. While previous AAA models have used elastin-disrupting techniques for aneurysm induction, the single use of elastase in many of these models does not account for the ongoing immune response against elastin and its degradation products (EDP). To model this ongoing immune response, we developed a model that sensitizes C57BL/6 mice to EDP by subcutaneously injecting EDP 7 days prior to aneurysm induction surgery. Aneurysm induction surgery proceeds with exposure of the abdominal aorta and application of topical elastase in the periaortic compartment, with the intention to expose elastin and EDP on the mouse aorta. With these moieties exposed, the animal should mount an immune response against these antigens to which it was previously sensitized. Repeat "booster" EDP injection 7 days later serves to propagate this immune response. Herein, we describe the protocol for the reliable creation of AAA in C57BL/6 mice via multiple sensitizations with EDP, followed by AAA induction surgery with perivascular elastase application. This model can be created quickly and at moderate cost, while inducing >30% aortic dilation in 82% of mice by video micrometry and 73% by ultrasound measurement, and >50% dilation in 64% by video micrometry and 27% by ultrasound, as measured at day 21 post-induction surgery. This technique is also associated with a 95% intraoperative survival rate.