IBiTech-bioMMeda, Ghent University-iMinds Medical IT, De Pintelaan 185 Blok B, 9000 Ghent, Belgium.
Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Cardiovasc Res. 2017 Aug 1;113(10):1230-1242. doi: 10.1093/cvr/cvx128.
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.
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 (r2 = 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.
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.
血管紧张素 II 输注的载脂蛋白 E 基因敲除（ApoE-/-）小鼠是用于临床前动脉瘤研究的一种流行的小鼠模型。在这里，我们深入了解了这些小鼠中经常报道但很少解释的夹层动脉瘤形状变化的原因。
共对 45 个离体主动脉进行了体外相位对比 X 射线断层显微镜扫描。在接受血管紧张素 II 输注 3 天后处死的 11 只小鼠的腹腔动脉和肠系膜动脉口附近检测到微破裂。在较晚的时间点（10、18 和 28 天后），根据是否存在中膜撕裂（31/31）、壁内血肿（23/31）或假腔（11/23），将胸腹部病变的形状变化分为 7 种不同的类型。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为常见。血肿的轴向长度与破裂的分支口总数密切相关（r2=0.78），在 23 只存在血肿的小鼠中，左侧肾上腺上动脉的口破裂。未形成壁内血肿的小鼠的肠系膜上动脉直径明显较低，并且假腔内的形成取决于中膜撕裂的位置，而不是长度。
基于我们的观察，我们提出了一个详细的假设，解释了主动脉侧支（i）如何影响中膜撕裂的起始和传播，以及随后的外膜夹层形成，以及（ii）如何影响夹层动脉瘤的形状变化。通过对在 micro-CT 成像过程中形成的夹层动脉瘤的活体可视化，我们部分验证了该假设，并得出结论，与研究腹主动脉瘤相比，血管紧张素 II 输注的小鼠更适合研究主动脉夹层。
