Abstract Body: Introduction: Abdominal aortic aneurysm (AAA) is a progressive infrarenal aortic dilation accounting for >167,200 deaths annually. In ~80% of AAA patients, a platelet laden intraluminal thrombus (ILT) forms in the aneurysm. While thrombosis may stabilize the aorta initially, progressive ILT accumulation is positively associated with aortic rupture, but a causal relationship has not yet been established. Platelet activation is linked to faster AAA growth and anti-platelet therapy shows pre-clinical benefit, yet no pharmacologic therapies are approved for AAA patients. Here, we characterize the temporal relationship between aneurysm growth and ILT formation in a murine model featuring ILT and test whether aspirin (ASA) intervention limits ILT expansion.
Methods and Results: Male C57BL/6J mice (10-14 weeks) received 0.2% BAPN in drinking water for 1 week before laparotomy, when 10mg/mL elastase (El+B, n=13) or heat inactivated elastase (Hl+B, n=5) was applied to the infrarenal aorta. BAPN water was maintained throughout the study. Bi-weekly 3D color Doppler imaging (VisualSonics Vevo F2) showed severe aortic dilation with disturbed and stagnant blood flow at the elastase-treated segment. ILTs formed distal to perturbed blood flow in 3/13, 9/13 and 12/13 mice at 2-, 4-, and 8-weeks post laparotomy respectively. Aneurysms with ILT were larger and grew faster. After 8 weeks, mice were euthanized and aneurysms were OCT-embedded, serially sectioned, and stained for CD41-platelets, CD68-macrophages, MPO-neutrophils, and αSMA-VSMCs. Confocal imaging confirmed ILT formation with marked platelet, macrophage, and neutrophil accumulation. Next, at 4 weeks post-laparotomy, El+B mice with similar aortic diameters were randomized to low dose ASA (30mg/L, El+B+ASA) or vehicle (El+B+Pl) in 0.2% BAPN water and followed for 16 weeks post intervention with bi-weekly ultrasounds. Aneurysm burden did not differ between El+B+ASA and El+B+Pl groups. Surprisingly, El+B+ASA mice experienced aortic rupture (5/7) at a significantly higher rate compared to El+B+Pl mice (0/6). Mice that underwent rupture exhibited an acute increase in aortic growth rate prior to death.
Conclusions: In this ILT murine AAA model, progressive thrombus formation parallels accelerated aneurysm growth and precedes rupture, but delayed low-dose ASA fails to reduce aneurysm burden while markedly increasing rupture, suggesting ASA may destabilize the aneurysmal aorta in this setting.