Thirugnanasambandam Mirunalini, Simionescu Dan T., Escobar Patricia G., Sprague Eugene, Goins Beth, Clarke Geoffrey D., Han Hai-Chao, Amezcua Krysta L., Adeyinka Oluwaseun R., Goergen Craig J., Finol Ender
UTSA/UTHSA Joint Graduate Program in Biomedical , Engineering, , University of Texas at San Antonio, , San Antonio, TX 78249
Department of Bioengineering, , Clemson University, , Clemson, SC 29634
J Biomech Eng. 2018 Aug 1;140(8):0845021-9. doi: 10.1115/1.4040398.
An abdominal aortic aneurysm (AAA) is a permanent localized expansion of the abdominal aorta with mortality rate of up to 90% after rupture. AAA growth is a process of vascular degeneration accompanied by a reduction in wall strength and an increase in inflammatory activity. It is unclear whether this process can be intervened to attenuate AAA growth, and hence, it is of great clinical interest to develop a technique that can stabilize the AAA. The objective of this work is to develop a protocol for future studies to evaluate the effects of drug-based therapies on the mechanics and inflammation in rodent models of AAA. The scope of the study is limited to the use of pentagalloyl glucose (PGG) for aneurysm treatment in the calcium chloride rat AAA model. Peak wall stress (PWS) and matrix metalloproteinase (MMP) activity, which are the biomechanical and biological markers of AAA growth and rupture, were evaluated over 4 weeks in untreated and treated (with PGG) groups. The AAA specimens were mechanically characterized by planar biaxial tensile testing and the data fitted to a five-parameter nonlinear, hyperelastic, anisotropic Holzapfel–Gasser–Ogden (HGO) material model, which was used to perform finite element analysis (FEA) to evaluate PWS. Our results demonstrated that there was a reduction in PWS between pre- and post-AAA induction FEA models in the treatment group compared to the untreated group using either animal-specific or average material properties. However, this reduction was not statistically significant. Conversely, there was a statistically significant reduction in MMP-activated fluorescent signal between pre- and post-AAA induction models in the treated group compared to the untreated group. Therefore, the primary contribution of this work is the quantification of the stabilizing effects of PGG using biomechanical and biological markers of AAA, thus indicating that PGG could be part of a new clinical treatment strategy that will require further investigation.
腹主动脉瘤（AAA）是腹主动脉的永久性局部扩张，破裂后的死亡率高达90%。AAA的生长是一个血管退化的过程，伴随着壁强度的降低和炎症活动的增加。目前尚不清楚这个过程是否可以通过干预来减缓AAA的生长，因此，开发一种能够稳定AAA的技术具有重大的临床意义。这项工作的目的是制定一个未来研究的方案，以评估基于药物的治疗方法对AAA啮齿动物模型力学和炎症的影响。该研究的范围仅限于在氯化钙诱导的大鼠AAA模型中使用五倍没食子酰葡萄糖（PGG）治疗动脉瘤。在未经治疗和接受治疗（使用PGG）的组中，对作为AAA生长和破裂生物力学及生物学标志物的峰值壁应力（PWS）和基质金属蛋白酶（MMP）活性进行了4周的评估。通过平面双轴拉伸试验对AAA标本进行力学表征，并将数据拟合到一个五参数非线性、超弹性、各向异性的霍尔扎佩尔 - 加塞尔 - 奥格登（HGO）材料模型，该模型用于进行有限元分析（FEA）以评估PWS。我们的结果表明，与未治疗组相比，使用动物特异性或平均材料特性时，治疗组在AAA诱导前后的FEA模型之间PWS有所降低。然而，这种降低没有统计学意义。相反，与未治疗组相比，治疗组在AAA诱导前后模型之间MMP激活的荧光信号有统计学意义的降低。因此，这项工作的主要贡献是使用AAA的生物力学和生物学标志物对PGG的稳定作用进行了量化，从而表明PGG可能是一种新的临床治疗策略的一部分，这将需要进一步研究。
