Loss of mural cells leads to wall degeneration, aneurysm growth, and eventual rupture in a rat aneurysm model.

Marbacher, Serge; Marjamaa, Johan; Bradacova, Katerina; von Gunten, Michael; Honkanen, Petri; Abo-Ramadan, Usama; Hernesniemi, Juha; Niemelä, Mika; Frösen, Juhana (2014). Loss of mural cells leads to wall degeneration, aneurysm growth, and eventual rupture in a rat aneurysm model. Stroke, 45(1), pp. 248-254. American Heart Association 10.1161/STROKEAHA.113.002745

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BACKGROUND AND PURPOSE

The biological mechanisms predisposing intracranial saccular aneurysms to growth and rupture are not yet fully understood. Mural cell loss is a histological hallmark of ruptured cerebral aneurysms. It remains unclear whether mural cell loss predisposes to aneurysm growth and eventual rupture.

METHODS

Sodium dodecyl sulfate decellularized and nondecellularized saccular aneurysm from syngeneic thoracic aortas were transplanted to the abdominal aorta of Wistar rats. Aneurysm patency and growth was followed up for 1 month with contrast-enhanced serial magnetic resonance angiographies. Endoscopy and histology of the aneurysms were used to assess the role of periadventitial environment, aneurysm wall, and thrombus remodeling.

RESULTS

Nondecellularized aneurysms (n=12) showed a linear course of thrombosis and remained stable. Decellularized aneurysms (n=12) exhibited a heterogeneous pattern of thrombosis, thrombus recanalization, and growth. Three of the growing aneurysms (n=5) ruptured during the observation period. Growing and ruptured aneurysms demonstrated marked adventitial fibrosis and inflammation, complete wall disruption, and increased neutrophil accumulation in unorganized intraluminal thrombus.

CONCLUSIONS

In the presented experimental setting, complete loss of mural cells acts as a driving force for aneurysm growth and rupture. The findings suggest that aneurysms missing mural cells are incapable to organize a luminal thrombus, leading to recanalization, increased inflammatory reaction, severe wall degeneration, and eventual rupture.

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