In situ decellularization of a large animal saccular aneurysm model: sustained inflammation and active aneurysm wall remodeling
Department of Radiology, New England Center for Stroke Research; Department of Radiology, Laboratory of Molecular Imaging Probes
Cardiovascular Diseases | Nervous System Diseases | Neurology | Radiology
OBJECTIVE: To investigate in situ decellularization of a large animal model of saccular aneurysm as a strategy for achieving aneurysmal growth and lasting inflammation.
METHODS: 18 New Zealand White rabbits were randomized 2:1 to receive endoluminal sodium dodecyl sulfate infusion (SDS, 1% solution, 45 min) following elastase or elastase-only treatment (control). All aneurysms were measured by digital subtraction angiography every 2 weeks. Every 2 weeks, three of the rabbits (two elastase + SDS, one control) underwent MRI, followed by contrast injection with myeloperoxidase (MPO)-sensing contrast agent. MRI was repeated 3 hours after contrast injection and the enhancement ratio (ER) was calculated. Following MRI, aneurysms were explanted and subjected to immunohistopathology.
RESULTS: During follow-up MRI, the average ER for SDS-treated animals was 1.63+/-0.20, compared with 1.01+/-0.06 for controls (p < 0.001). The width of SDS-treated aneurysms increased significantly in comparison with the elastase aneurysms (47% vs 20%, p < 0.001). Image analysis of thin sections showed infiltration of MPO-positive cells in decellularized aneurysms and surroundings through the 12-week observation period while control tissue had 5-6 times fewer cells present 2 weeks after aneurysm creation. Immunohistochemistry demonstrated the presence of MPO-positive cells surrounding decellularized lesions at early time points. MPO-positive cells were found in the adventitia and in the thrombi adherent to the aneurysm wall at later time points.
CONCLUSIONS: In situ decellularization of a large animal model of saccular aneurysms reproduces features of unstable aneurysms, such as chronic inflammation (up to 12 weeks) and active aneurysm wall remodeling, leading to continued growth over 8 weeks.
MRI, aneurysm, inflammation
DOI of Published Version
King RM, Caroff J, Langan ET, Leporati A, Rodriguez-Rodriguez A, Raskett CM, Gupta S, Puri AS, Caravan P, Gounis MJ, Bogdanov AA Jr. In situ decellularization of a large animal saccular aneurysm model: sustained inflammation and active aneurysm wall remodeling. J Neurointerv Surg. 2020 Oct 5:neurintsurg-2020-016589. doi: 10.1136/neurintsurg-2020-016589. Epub ahead of print. PMID: 33020207. Link to article on publisher's site
Journal of neurointerventional surgery
King RM, Caroff J, Langan ET, Leporati AM, Rodriguez-Rodriguez A, Raskett CM, Gupta S, Puri AS, Caravan P, Gounis MJ, Bogdanov AA. (2020). In situ decellularization of a large animal saccular aneurysm model: sustained inflammation and active aneurysm wall remodeling. Radiology Publications. https://doi.org/10.1136/neurintsurg-2020-016589. Retrieved from https://escholarship.umassmed.edu/radiology_pubs/580