Based on our observations we propose an elaborate hypothesis that explains how aortic side branches (i) affect the initiation and propagation of medial tears and the subsequent adventitial dissection and (ii) affect the variability in shape of dissecting aneurysms. This hypothesis was partially validated through the live visualization of a dissecting aneurysm that formed during micro-CT imaging, and led us to the conclusion that angiotensin II-infused mice are more clinically relevant for the study of aortic dissections than for the study of abdominal aortic aneurysms.
A ortic aneurysm is clinically defined as a local increase in aortic diameter of at least 50% compared with the normal diameter.1 Abdominal aortic aneurysms (AAA) are associated with cardiovascular risk factors, such as smoking, age, male sex, hyperlipidemia, hypertension, and chronic obstructive pulmonary disease.2 Although these factors also underlie the majority of thoracic aortic aneurysms, the latter subgroup incidence is more often related to family history than to the above mentioned factors.3 Because most aneurysms remain asymptomatic until-often fatal-complications such as rupture occur, our understanding of the pathogenesis, especially in early stages, is limited. Angiotensin II infusion into hypercholesterolemic ApoE −/− mice is a well-known experimental model of both AAAs 4 and thoracic aortic aneurysms. 5 We have recently explored a novel imaging technique, phase contrast X-ray tomographic microscopy (PCXTM), to visualize the abdominal lesions of angiotensin II-infused mice. 6 Because the axial resolution of our PCXTM scans (6.5 μm) was close to the thickness of histological coupes for routine morphological evaluation (4 μm), we introduced PCXTM-guided histology to select sections of the aorta in a highly precise manner for pathology analysis. 6 This approach allowed us to demonstrate that the abdominal lesions in these mice stem from medial ruptures in the suprarenal side branches, leading to media-adventitia dissection with intramural bleeding and thrombus formation. 6 Much like in humans, data on thoracic aortic aneurysms are scarcer than data on AAAs in mouse models. Daugherty et al reported dilatation of the ascending aorta as semiquantified on histological sections after 28 days of continuous angiotensin II infusion in ApoE −/− mice. 5 They observed expansion of interlaminar spaces, collagen deposition, and macrophage © 2016 American Heart Association, Inc. Objective-To understand the anatomy and physiology of ascending aortic aneurysms in angiotensin II-infused ApoE −/− mice. Approach and Results-We combined an extensive in vivo imaging protocol (high-frequency ultrasound and contrastenhanced microcomputed tomography at baseline and after 3, 10, 18, and 28 days of angiotensin II infusion) with synchrotron-based ultrahigh resolution ex vivo imaging (phase contrast X-ray tomographic microscopy) in n=47 angiotensin II-infused mice and 6 controls. Aortic regurgitation increased significantly over time, as did the luminal volume of the ascending aorta. In the samples that were scanned ex vivo, we observed one or several focal dissections, with the largest located in the outer convex aspect of the ascending aorta. The volume of the dissections moderately correlated to the volume of the aneurysm as measured in vivo (r 2 =0.46). After 3 days of angiotensin II infusion, we found an interlaminar hematoma in 7/12 animals, which could be linked to an intimal tear. There was also a significant increase in single laminar ruptures, which may have facilitated a progressive enlargement of the focal dis...
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