Background: Abdominal Aortic Aneurysm (AAA) is defined as an irreversible arterial wall dilation with a diameter >50% and characterized by thinning and weakness of the vascular wall. In humans, aneurysms are associated with intramural thrombus and are prone to rupture which result in death. Thrombi from AAA patients are highly enriched in leukocytes and bacteria, eg. Porphyromonas gingivalis (Pg). This leukocyte-rich thrombus is considered the driving force of vessel wall rupture. Beyond their role in aneurysmal thrombus formation, platelets support leukocyte recruitment and interact with bacteria. This cross-talk is an important feature in thrombo-inflammatory vascular disease.

Aims: To decipher the role of platelets in intraluminal thrombosis in AAA

Methods: AAA was induced by applying an elastase-soaked filter paper on the infrarenal abdominal aorta of WT mice and mice lacking the GPIbα subunit of the platelet receptor for von Willebrand factor hIL4R/GPIbα mice, the ADP receptor P2Y12, or the thrombin receptor PAR4.

Results: In elastase-treated WT mice, an early recruitment of platelets and leukocytes to the damaged vessel wall is observed by intravital microscopy. No thrombi were observed by histology. Histological analysis of elastase-treated WT mice injected with Pg, showed large thrombi in the dilated vessel wall in 70% of the mice (9 out of 13 mice). These thrombi were enriched in platelets, leukocytes and neutrophil extracellular traps. Similar to WT mice, intraluminal thrombosis occurred in 67% of hIL4/GPIbα mice (3 out of 5). P2Y12 deficient mice showed an incidence of 50% (2 out of 4) of intraluminal thrombosis. Remarkably, PAR4 null mice have a significant reduced intraluminal incidence thrombosis of 25% (1 out of 4 mice).

Conclusions: We established a novel mouse model of AAA with an intraluminal thrombus. Unlike the GPIbα and PY12 receptors, our data suggest that PAR4 plays a critical role to the intraluminal thrombus formation and platelet activation in Pg-injected mice.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/development-of-a-novel-mouse-model-of-abdominal-aortic-aneurysm-with-intraluminal-thrombus/