Haskett Darren, Azhar Mohamad, Utzinger Urs, Vande Geest Jonathan P
Graduate Interdisciplinary Program of Biomedical Engineering; University of Arizona; Tucson, AZ USA.
Developmental Biology and Neonatal Medicine Program, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN USA.
Biomatter. 2013 Jul-Sep;3(3). doi: 10.4161/biom.24648. Epub 2013 Apr 1.
AAA is a complex disease that leads to a localized dilation of the infrarenal aorta that develops over years. Longitudinal information in humans has been difficult to obtain for this disease, therefore mouse models have become increasingly used to study the development of AAAs. The objective of this study was to determine any changes that occur in the biomechanical response and fiber microstructure in the ApoE(-/-) AngII mouse model of aneurysm during disease progression. Adult ApoE(-/-) AngII infused mice along with wild-type controls were taken at 14 and 28 d. Aortas were excised and tested simultaneously for biaxial mechanical response and ECM organization. Data sets were fit to a Fung-type constitutive model to give peak strains and stiffness values. Images from two photon microscopy were quantified in order to assess the preferred fiber alignment and degree of fiber orientation. Biomechanical results found significant differences that were present at 14 d had returned to normal by 28 d along with significant changes in fiber orientation and dispersion indicating remodeling occurring within the aneurysmal wall. This return of some of the normal biomechanical function, in addition the continuing changes that occur in the microstructure suggest a restorative response that occurs in the ApoE(-/-) AngII infused model after the initial aneurysm formation.
腹主动脉瘤是一种复杂的疾病，会导致肾下腹主动脉局部扩张，且这种扩张会持续数年。由于很难获取人类关于这种疾病的纵向信息，因此小鼠模型越来越多地被用于研究腹主动脉瘤的发展。本研究的目的是确定在疾病进展过程中，载脂蛋白E基因敲除（ApoE(-/-)）血管紧张素II（AngII）小鼠动脉瘤模型的生物力学反应和纤维微观结构发生的任何变化。在第14天和第28天处死成年ApoE(-/-) AngII灌注小鼠以及野生型对照小鼠。切除主动脉并同时测试其双轴力学反应和细胞外基质组织。将数据集拟合到Fung型本构模型以得出峰值应变和刚度值。对双光子显微镜图像进行量化，以评估纤维的优先排列方向和纤维取向程度。生物力学结果发现，在第14天出现的显著差异在第28天已恢复正常，同时纤维取向和分散度也发生了显著变化，表明动脉瘤壁内正在发生重塑。一些正常生物力学功能的恢复，以及微观结构中持续发生的变化，表明在最初形成动脉瘤后，ApoE(-/-) AngII灌注模型中发生了修复反应。
