A murine model of thoracic aortic aneurysms
A murine model of thoracic aortic aneurysms
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DOI：
10.1016/s0022-4804(03)00193-8
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发表时间：
2003-11-01
影响因子：
2.2
通讯作者：
Spinale, FG
中科院分区：
文献类型：
--
作者：
Ikonomidis, JS;Gibson, WC;Spinale, FG
背景。胸主动脉瘤（TAA）形成的机制尚不清楚，主要是由于缺乏有用且可重复的模型。因此，本研究的目的是验证腹腔应用氯化钙（CaCl2）可以在小鼠体内产生TAAs的假设。材料和方法。对成年129/SvE小鼠（n = 8）麻醉，经左开胸暴露胸主动脉。CaCl2 （0.5M）作用于远段降主动脉15分钟后闭胸。4周时，从肾动脉根部取灌注固定的主动脉。用共聚焦显微镜测量直径，用苏木精和伊红染色切片测量壁厚。对照组（n = 15）胸降主动脉远端内径为0.60 +/- 0.04 mm， CaCl2治疗后增加25% （0.76 +/- 0.06 mm, P < 0.05）。对照主动脉壁厚为48 +/- 9 μ m，相应cacl2暴露段壁厚降低47% （25 8 μ m, P < 0.05）。两组间升主动脉直径和壁厚（作为内对照）无显著差异。TAA的小天狼星红染色显示胶原破坏和板层组织破坏。我们的结论是，经腔内应用CaCl2至胸主动脉可导致扩张、壁薄和壁结构破坏，这是动脉瘤形成的标志。据我们所知，这些发现首次描述了小鼠系统中孤立TAA形成的可重复模型的生成。(C) 2003 Elsevier Inc.版权所有。
Background. The mechanisms of thoracic aortic aneurysm (TAA) formation are poorly understood, mainly due to the lack of a useful and reproducible model. Accordingly, the goal of this study was to test the hypothesis that abluminal calcium chloride (CaCl2) application could create TAAs in the mouse.Materials and methods. Adult 129/SvE mice (n = 8) were anesthetized and their thoracic aortas exposed via left thoracotomy. CaCl2 (0.5M) was applied to the distal descending thoracic aorta for 15 min followed by chest closure. At 4 weeks, the perfusion-fixed aorta was harvested from the root to the renal arteries. Diameter measurements were made using confocal microscopy, and wall thickness was measured from hematoxylin and eosin-stained sections.Results. The control (n = 15) distal descending thoracic aortic diameter was 0.60 +/- 0.04 mm and increased by 25% (0.76 +/- 0.06 mm, P < 0.05) following CaCl2 treatment. Control aortic wall thickness was 48 +/- 9 mum and decreased by 47% in corresponding CaCl2-exposed segments (25 8 mum, P < 0.05). The diameter and wall thickness of the ascending aorta (used as an internal control) were not significantly different between groups. Picrosirius red staining of the TAA showed adventitial collagen breakdown and disruption of lamellar organization.Conclusions. We conclude that abluminal application of CaCl2 to the thoracic aorta reliably produces dilation, wall-thinning, and disruption of mural architecture, the hallmark signs of aneurysm formation. To our knowledge, these findings describe for the first time the generation of a reproducible model of isolated TAA formation in a murine system. (C) 2003 Elsevier Inc. All rights reserved.