Graduate Interdisciplinary Program of Biomedical Engineering, The University of Arizona, Tucson, AZ 85721-0119, USA.
J Biomech. 2012 Mar 15;45(5):772-9. doi: 10.1016/j.jbiomech.2011.11.017. Epub 2011 Dec 23.
Abdominal aortic aneurysm (AAA) is a complex disease that leads to a localized dilation of the infrarenal aorta, the rupture of which is associated with significant morbidity and mortality. Animal models of AAA can be used to study how changes in the microstructural and biomechanical behavior of aortic tissues develop as disease progresses in these animals. We chose here to investigate the effect of angiotensin II (AngII) in C57BL/6 mice as a first step towards understanding how such changes occur in the established ApoE(-/-) AngII infused mouse model of AAA.
The objective of this study was to utilize a recently developed device in our laboratory to determine how the microstructural and biomechanical properties of AngII-infused C57BL/6 wildtype mouse aorta change following 14 days of AngII infusion.
C57BL/6 wildtype mice were infused with either saline or AngII for 14 day. Aortas were excised and tested using a device capable of simultaneously characterizing the biaxial mechanical response and load-dependent (unfixed, unfrozen) extracellular matrix organization of mouse aorta (using multiphoton microscopy). Peak strains and stiffness values were compared across experimental groups, and both datasets were fit to a Fung-type constitutive model. The mean mode and full width at half maximum (FWHM) of fiber histograms from two photon microscopy were quantified in order to assess the preferred fiber distribution and degree of fiber splay, respectively.
The axial stiffness of all mouse aorta was found to be an order of magnitude larger than the circumferential stiffness. The aortic diameter was found to be significantly increased for the AngII infused mice as compared to saline infused control (p=0.026). Aneurysm, defined as a percent increase in maximum diameter of 30% (defined with respect to saline control), was found in 3 of the 6 AngII infused mice. These three mice displayed adventitial collagen that lacked characteristic fiber crimp. The biomechanical response in the AngII infused mice showed significantly reduced circumferential compliance. We also noticed that the ability of the adventitial collagen fibers in AngII infused mice to disperse in reaction to circumferential loading was suppressed.
Collagen remodeling is present following 14 days of AngII infusion in C57BL/6 mice. Aneurysmal development occurred in 50% of our AngII infused mice, and these dilatations were accompanied with adventitial collagen remodeling and decreased circumferential compliance.
腹主动脉瘤（AAA）是一种复杂的疾病，导致肾下主动脉局部扩张，破裂可导致显著的发病率和死亡率。AAA 的动物模型可用于研究随着这些动物疾病的进展，主动脉组织的微观结构和生物力学行为如何发生变化。我们选择在这里研究血管紧张素 II（AngII）在 C57BL/6 小鼠中的作用，作为了解在已建立的 ApoE（-/-）AngII 输注型 AAA 小鼠模型中发生这种变化的第一步。
本研究的目的是利用我们实验室最近开发的一种设备，确定 AngII 输注 14 天后 C57BL/6 野生型 AngII 输注小鼠主动脉的微观结构和生物力学特性如何变化。
C57BL/6 野生型小鼠接受盐水或 AngII 输注 14 天。取出主动脉并使用能够同时表征小鼠主动脉的双轴力学响应和负载依赖性（未固定、未冻结）细胞外基质组织的设备进行测试（使用多光子显微镜）。比较实验组之间的峰值应变和刚度值，并将两个数据集拟合到 Fung 型本构模型中。为了评估纤维的优选分布和纤维张开的程度，从双光子显微镜量化纤维直方图的平均模式和半峰全宽（FWHM）。
所有小鼠主动脉的轴向刚度都比周向刚度大一个数量级。与盐水输注对照相比，AngII 输注小鼠的主动脉直径显著增加（p=0.026）。在 6 只 AngII 输注小鼠中，有 3 只出现了动脉瘤，定义为最大直径增加 30%（相对于盐水对照）。这 3 只小鼠的外膜胶原缺乏特征性的纤维卷曲。AngII 输注小鼠的周向顺应性的生物力学反应显示出明显降低。我们还注意到，AngII 输注小鼠的外膜胶原纤维在应对周向加载时分散的能力受到抑制。
在 C57BL/6 小鼠中，AngII 输注 14 天后存在胶原重塑。我们 AngII 输注小鼠中有 50%发生了动脉瘤，这些扩张伴随着外膜胶原重塑和周向顺应性降低。
