Aortotomy-induced acute mural thrombosis progresses to saccular aneurysm formation

Current models of arterial thrombus frequently rely on chemical or mechanical injury and often cause total vessel occlusion, limiting their relevance as a model of early events. To address this, we developed a reproducible mouse model of mural thrombus induced by an aortotomy.

A 1-mm aortotomy was created in the mouse abdominal aorta using a 31-gauge needle, and then the site was covered with autologous adipose tissue using gentle pressure for hemostasis. Arterial mural thrombus with an arteriovenous fistula was created by using a 25-gauge needle puncturing from the mouse aorta into the inferior vena cava. Thrombus formation and vessel remodeling were assessed via histology, immunofluorescence, and scanning electron microscopy up to 90 days. We also evaluated the effect of local delivery of rapamycin and β-aminopropionitrile.

Acute mural thrombus formation occurred immediately after aortotomy, followed by endothelial and smooth muscle cell infiltration by day 7. Most thrombi regressed by day 21, and the vessel wall closely resembled native aorta after 6 weeks. Rapamycin and β-aminopropionitrile were associated with increased mural thrombus size. All aortotomies developed saccular aneurysms that dilated gradually over 21 days. Rapamycin was also associated with increased arterial mural thrombus size with arteriovenous fistula.

The aortotomy model replicates mural thrombus initiation, resolution, and wall remodeling without complete vessel occlusion. This mouse model offers a robust platform for investigating mural thrombosis, vascular healing, and aneurysm biology.