Loss of Mural Cells Leads to Wall Degeneration, Aneurysm Growth, and Eventual Rupture in a Rat Aneurysm Model

Abstract

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.

Evolution of Flow-Diverter Endothelialization and Thrombus Organization in Giant Fusiform Aneurysms after Flow Diversion: A Histopathologic Study

“…Clinical experience and experimental evidence have shown that the loss of mural cells is associated with an inability to transform intraluminal thrombus to stable scar tissue because of the lack of smooth muscle cells inside the wall. 28 Subsequently, the lack of thrombus organization is likely to be related to cellular loss of the sick wall in our GFAs.…”

Intraluminal Cell Transplantation Prevents Growth and Rupture in a Model of Rupture-Prone Saccular Aneurysms

“…The saccular aneurysms to be decellularized before use in thrombus-induced decellularized aneurysms and thrombus-induced decellularized smooth muscle cell-transplanted aneurysms groups were processed as described in detail previously. 10,11 Briefly, donor grafts were harvested and frozen in PBS at −4°C. The next day the grafts were thawed, incubated for 10 hours at 37°C in 0.1% sodium dodecyl sulfate (SDS), and finally refrozen until use.…”

“…Existing protocols for high-resolution time-of-flight MRA 12 and CE-MRA 11 were performed. CE-MRA were analyzed and scored for the rate of thrombosis as described previously, with slight modification ( Figure IV in the online-only Data Supplement) 11,13 : 0=no recurrence (no filling); 1=partial recurrence (<50% filling); and 2=complete recurrence (>50% filling). Growing aneurysms were further analyzed using 3-dimensional active contour segmentation software itk-SNAP (V2.4, Pennsylvania, PA).…”

The Helsinki Rat Microsurgical Sidewall Aneurysm Model

“…With the exception of a single case significant growth or dilatation of the experimental aneurysms was not observed and none of them ruptured 3 . However, if the harvested grafts are decellularized the aneurysms demonstrate a heterogeneous pattern of thrombosis, recanalization, growth, and eventual rupture 11 . Growing aneurysms in the latter study demonstrated marked adventitial fibrosis and inflammation, complete wall disruption, and increased neutrophil accumulation in unorganized intraluminal thrombus.…”