Angiotensin II infusion into ApoE-/- mice: a model for aortic dissection rather than abdominal aortic aneurysm?
Angiotensin II infusion into ApoE-/- mice: a model for aortic dissection rather than abdominal aortic aneurysm?
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DOI：
10.1093/cvr/cvx128
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发表时间：
2017-08-01
影响因子：
10.8
通讯作者：
Segers, Patrick
中科院分区：
文献类型：
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作者：
Trachet, Bram;Aslanidou, Lydia;Segers, Patrick
血管紧张素II（Angiotensin II）灌注的ApoE（-/-）小鼠是临床前动脉瘤研究的常用小鼠模型。在这里，我们提供的洞察力，经常报告，但很少解释的变异性，在这些mixtes.Methods和结果的夹层动脉瘤的形状进行了扫描离体与相位衬度X-射线断层扫描显微镜N=45。在血管紧张素II输注3天后处死的8/11只小鼠中，在腹腔动脉和肠系膜动脉口附近检测到微破裂。在随后的时间点（10、18和28天后），根据是否存在内侧撕裂（31/31）、壁内血肿（23/31）或假通道（11/23），将胸腹部病变（发生在31/34只小鼠中）形状的变异性分为7个不同类别。在胸主动脉和腹主动脉中均检测到中膜撕裂，在腹腔动脉和肠系膜动脉的左侧和腹侧最常见。血肿的轴向长度与破裂的分支开口总数密切相关（r（2）= 0.78），在23只血肿小鼠中，22只左肾上腺动脉开口破裂。对于未发生壁内血肿的小鼠，基线时的腹腔上直径显著较低，并且壁内血肿内假通道的形成取决于位置，而不是长度，结论根据我们的观察，我们提出了一个详细的假设，解释了主动脉侧支（i）影响中膜撕裂和后续外膜夹层的起始和传播，以及（ii）影响夹层动脉瘤形状的变异性。通过显微CT成像过程中形成的夹层动脉瘤的实时可视化部分验证了这一假设，并使我们得出结论，血管紧张素II输注小鼠与腹主动脉瘤研究相比，与主动脉夹层研究更具临床相关性。
Aims Angiotensin II-infused ApoE(-/-) mice are a popular mouse model for preclinical aneurysm research. Here, we provide insight in the often-reported but seldom-explained variability in shape of dissecting aneurysms in these mice.Methods and results N=45 excised aortas were scanned ex vivo with phase-contrast X-ray tomographic microscopy. Micro-ruptures were detected near the ostium of celiac and mesenteric arteries in 8/11 mice that were sacrificed after 3 days of angiotensin II-infusion. At later time points (after 10, 18, and 28 days) the variability in shape of thoraco-abdominal lesions (occurring in 31/34 mice) was classified into 7 different categories based on the presence or absence of a medial tear (31/31), an intramural hematoma (23/31) or a false channel (11/23). Medial tears were detected both in the thoracic and the abdominal aorta and were most prevalent at the left and ventral aspects of celiac and mesenteric arteries. The axial length of the hematoma strongly correlated to the total number of ruptured branch ostia (r(2) = 0.78) and in 22/23 mice with a hematoma the ostium of the left suprarenal artery had ruptured. Supraceliac diameters at baseline were significantly lower for mice that did not develop an intramural hematoma, and the formation of a false channel within that intramural hematoma depended on the location, rather than the length, of the medial tear.Conclusion 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.