Comparison of 10 murine models reveals a distinct biomechanical phenotype in thoracic aortic aneurysms
Comparison of 10 murine models reveals a distinct biomechanical phenotype in thoracic aortic aneurysms
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DOI：
10.1098/rsif.2016.1036
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发表时间：
2017-05-01
影响因子：
3.9
通讯作者：
Humphrey, J. D.
中科院分区：
文献类型：
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作者：
Bellini, C.;Bersi, M. R.;Humphrey, J. D.
胸主动脉瘤是危及生命的病变，对年轻人和老年人都有影响。它们经常与基因突变相关，其特征是弹性纤维完整性降低、平滑肌细胞功能失调、胶原重塑不当和粘液物质聚集。迫切需要更好地了解这些基因突变导致主动脉结构完整性受损，并使主动脉壁容易扩张、剥离或破裂。在本文中，我们比较了 10 个小鼠模型的升主动脉的双轴力学特性：野生型对照、急性弹性蛋白酶处理以及八个具有影响细胞外基质蛋白、跨膜受体、细胞骨架蛋白或细胞内信号分子的基因突变的模型。总的来说，我们对这些不同小鼠模型的数据表明，机械功能的降低（如弹性能量存储能力降低或扩张性降低所表明的那样）不会导致动脉瘤。相反，尽管周向和轴向壁应力正常或低于正常，但易于发生动脉瘤的小鼠升主动脉的壁内细胞似乎无法维持或恢复固有的周向材料刚度，这可能使壁在生物力学上容易持续扩张并可能破裂。这一发现与细胞外基质潜在的机械感应或机械调节功能失调相一致，细胞外基质通常赋予细胞壁适当的顺应性和足够的强度。
Thoracic aortic aneurysms are life-threatening lesions that afflict young and old individuals alike. They frequently associate with genetic mutations and are characterized by reduced elastic fibre integrity, dysfunctional smooth muscle cells, improperly remodelled collagen and pooled mucoid material. There is a pressing need to understand better the compromised structural integrity of the aorta that results from these genetic mutations and renders the wall vulnerable to dilatation, dissection or rupture. In this paper, we compare the biaxial mechanical properties of the ascending aorta from 10 murine models: wildtype controls, acute elastase-treated, and eight models with genetic mutations affecting extracellular matrix proteins, transmembrane receptors, cytoskeletal proteins, or intracellular signalling molecules. Collectively, our data for these diverse mouse models suggest that reduced mechanical functionality, as indicated by a decreased elastic energy storage capability or reduced distensibility, does not predispose to aneurysms. Rather, despite normal or lower than normal circumferential and axial wall stresses, it appears that intramural cells in the ascending aorta of mice prone to aneurysms are unable to maintain or restore the intrinsic circumferential material stiffness, which may render the wall biomechanically vulnerable to continued dilatation and possible rupture. This finding is consistent with an underlying dysfunctional mechanosensing or mechanoregulation of the extracellular matrix, which normally endows the wall with both appropriate compliance and sufficient strength.