The Effect of Pentagalloyl Glucose on the Wall Mechanics and Inflammatory Activity of Rat Abdominal Aortic Aneurysms.
The Effect of Pentagalloyl Glucose on the Wall Mechanics and Inflammatory Activity of Rat Abdominal Aortic Aneurysms.
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五没食子酰葡萄糖对大鼠腹主动脉瘤壁力学和炎症活动的影响。
DOI：
10.1115/1.4040398
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Finol,Ender
中科院分区：
文献类型：
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作者：
Thirugnanasambandam,Mirunalini;Simionescu,DanT.;Escobar,PatriciaG.;Sprague,Eugene;Goins,Beth;Clarke,GeoffreyD.;Han,Hai-Chao;Amezcua,KrystaL.;Adeyinka,OluwaseunR.;Goergen,CraigJ.;Finol,Ender
腹主动脉瘤（AAA）是腹主动脉的永久性局部扩张，破裂后死亡率高达90%。AAA生长是伴随着壁强度降低和炎症活性增加的血管变性过程。目前尚不清楚是否可以干预该过程以减弱AAA生长，因此，开发一种可以稳定AAA的技术具有很大的临床意义。这项工作的目的是为未来的研究开发一个方案，以评估基于药物的治疗对AAA啮齿动物模型的力学和炎症的影响。本研究的范围仅限于在氯化钙大鼠AAA模型中使用五镓酰葡萄糖（PGG）进行动脉瘤治疗。峰值壁应力（PWS）和基质金属蛋白酶（MMP）活性，这是AAA生长和破裂的生物力学和生物学标志物，在4周内在未治疗和治疗（PGG）组中进行了评价。通过平面双轴拉伸试验对AAA样本进行机械表征，并将数据拟合至五参数非线性、超弹性、各向异性Holzapfel-Gasser-Ogden（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，使用动物特异性或平均材料特性，与未处理组相比，处理组中AAA诱导前后FEA模型的PWS减少。然而，这种减少在统计学上并不显著。相反，与未治疗组相比，治疗组中AAA诱导模型前后MMP激活的荧光信号在统计学上显著减少。因此，这项工作的主要贡献是使用AAA的生物力学和生物标志物量化PGG的稳定作用，从而表明PGG可能是需要进一步研究的新临床治疗策略的一部分。
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.