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Ultrasound And Histological Characteristics Of Suprarenal Aortic Aneurysms Induced By Angiotensin II In The Genetically Intact C57BL6 Mouse: An Approach To Studying Aneurysmal Disease Without The Influence Of Atherosclerosis

Leslie S Tyrie¹, Elisa E Konofagou², Kana Fujikura², Jianwen Luo², Sorin Selegean¹, Harold Gaetz¹, M David Tilson, III¹ ∙
¹Columbia University / St Lukes-Roosevelt Hospital Center, New York, NY; ²Columbia University, New York, NY

Objective: Slow release of Angiotensin II (AngII) from subcutaneous drug delivery capsules in ApoE knockout mice is a model for producing abdominal aortic aneurysms (AAAs). This model also induces hyperlipidemia and atherosclerotic plaques in the entire aorta, including the aneurysmal segment. With two ongoing processes, it is difficult to isolate cellular pathways specific for AAA disease. There has been one report that non-hyperlipidemic, wildtype (WT) mice also develop AAAs with AngII treatment. The present study reports confirmation of this model and describes additional features of ultrasound (US), gross, and microscopic findings. Methods: 27 (7-10 month old male WT C57BL6) mice were studied. Five served as sham controls and received saline capsules; 22 received AngII capsules. At 4 weeks, B-mode US measurements were done by a “blinded” observer. After euthanasia, the aortas were fixed in formalin, embedded in paraffin, and sectioned for staining with H&E and EVG. Results: One AngII-treated mouse died of autopsy-proven AAA rupture at day 26. Of the remaining 21 mice, 11 had obvious suprarenal AAAs ranging from 1.7-2.8x normal diameter. No sham mice had AAAs. The mean diameter of the AngII-induced AAAs was 2.33 +/- 0.17 mm compared to 1.18 +/- 0.17 mm (p<0.0001), measured in the non-dilated suprarenal aorta of the same animals. A thrombus component of the aortic pathology in many of the AAAs could be seen before sacrifice on ultrasound imaging. Histopathology of the AAAs revealed dissections in the sub-adventitial plane of the aorta and accounted for much of the observed aneurysmal expansion. The lesions were undergoing extensive remodeling and inflammatory infiltration at the time of observation at 28 days. Conclusions: 55% of the 22 ApoE +/+ WT mice developed aneurysmal dilations or died of rupture within 4 weeks of initiation with AngII infusion. This report shows it will be possible to investigate the pathobiology of Angiotensin II-induced AAA, without the confounding issues associated with hyperlipidemia and atherosclerosis in the ApoE -/- mouse. Further studies are indicated to characterize the early molecular and pathological mechanisms initiated by AngII.