Biomechanical consequences of compromised elastic fiber integrity and matrix cross-linking on abdominal aortic aneurysmal enlargement.
Biomechanical consequences of compromised elastic fiber integrity and matrix cross-linking on abdominal aortic aneurysmal enlargement.
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DOI：
10.1016/j.actbio.2021.07.059
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发表时间：
2021-10-15
影响因子：
9.7
通讯作者：
Humphrey JD
中科院分区：
文献类型：
--
作者：
Weiss D;Latorre M;Rego BV;Cavinato C;Tanski BJ;Berman AG;Goergen CJ;Humphrey JD
腹主动脉瘤（AAA）的组织病理学特征为弹性纤维完整性受损、平滑肌细胞或其功能丧失以及胶原蛋白重塑。我们使用了最近推出的小鼠模型AAAs，结合酶降解的弹性纤维和赖氨酰氧化酶的阻断，从而基质交联，研究进行性扩张的肾下腹主动脉，包括发展的管腔内血栓。我们量化了动脉瘤段内生物材料特性和生物力学功能的变化，作为扩张时间和血栓形成程度的函数。为此，我们将多模态成像与最先进的生物力学测试和组织学相结合，首次量化区域异质性，并使用动脉生长和重塑的计算模型来测试数据所提出的多个假设，这些假设涉及弹性蛋白丢失的程度、糖胺聚糖的积累和胶原蛋白周转率。我们发现，标准的组织病理学结果可能会产生误导，而结合先进的实验和计算方法显示，糖胺聚糖积累是病理性的，而不是适应性的，如果没有交联，胶原蛋白沉积增加是无效的。总之，弹性纤维完整性的丧失可能是主动脉瘤的一个强有力的引发因素，但纤维胶原重塑的速率和有效性决定了动脉瘤的扩大。
Abdominal aortic aneurysms (AAAs) are characterized histopathologically by compromised elastic fiber integrity, lost smooth muscle cells or their function, and remodeled collagen. We used a recently introduced mouse model of AAAs that combines enzymatic degradation of elastic fibers and blocking of lysyl oxidase, and thus matrix cross-linking, to study progressive dilatation of the infrarenal abdominal aorta, including development of intraluminal thrombus. We quantified changes in biomaterial properties and biomechanical functionality within the aneurysmal segment as a function of time of enlargement and degree of thrombosis. Towards this end, we combined multi-modality imaging with state-of-the art biomechanical testing and histology to quantify regional heterogeneities for the first time and we used a computational model of arterial growth and remodeling to test multiple hypotheses, suggested by the data, regarding the degree of lost elastin, accumulation of glycosaminoglycans, and rates of collagen turnover. We found that standard histopathological findings can be misleading, while combining advanced experimental and computational methods revealed that glycosaminoglycan accumulation is pathologic, not adaptive, and that heightened collagen deposition is ineffective if not cross-linked. In conclusion, loss of elastic fiber integrity can be a strong initiator of aortic aneurysms, but it is the rate and effectiveness of fibrillar collagen remodeling that dictates enlargement.
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影响因子：
5.3
作者：
Cavinato C;Murtada SI;Rojas A;Humphrey JD
通讯作者：
Humphrey JD
影响因子：
4.3
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Latorre M;Humphrey JD
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Humphrey JD
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1.7
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Humphrey JD
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Humphrey JD
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通讯作者：
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Humphrey, J. D.;Holzapfel, G. A.
通讯作者：
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