A novel chemo-mechano-biological model of arterial tissue growth and remodelling
A novel chemo-mechano-biological model of arterial tissue growth and remodelling
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DOI：
10.1016/j.jbiomech.2016.04.037
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发表时间：
2016-08-16
影响因子：
2.4
通讯作者：
Watton, Paul N.
中科院分区：
文献类型：
--
作者：
Aparicio, Pedro;Thompson, Mark S.;Watton, Paul N.
动脉生长和重塑(G&R)是由血管细胞对其化学和机械环境的反应所介导的。到目前为止，机械刺激和生化刺激往往是分开建模的，然而这忽略了它们复杂的相互作用。在这里，我们提出了一个新的动脉化学-机械-生物学的数学模型。我们举例说明了它在人降主动脉炎性动脉瘤的发展中的应用。动脉壁被建模为一个双层的圆柱形非线性弹性膜，它被内部加压和轴向拉伸。伴随着动脉瘤发展的中层退化是由炎症反应驱动的。胶原蛋白的重塑是通过适应成分的自然参考构型来模拟的；生长是通过标准化质量密度的变化来模拟的。我们解释了胶原蛋白纤维被配置到基质中的附着伸展的分布，并创新地允许这种分布重新建模。这使得能够模拟外膜不断变化的功能角色。成纤维细胞介导的胶原生长用生化途径模型表示：在基质沉积的关键促进剂转化生长因子(TGF)-β的调控下，成纤维细胞特性和关键生物分子水平的演化由一个耦合的非线性ODE系统控制。给定生理上现实的靶点，可以捕捉到不同的动脉瘤发展模式，而生化变量的预测演化与实验观察到的趋势定性一致。有趣的是，我们观察到增加促进胶原的转化生长因子-β水平可以阻止动脉瘤的生长，这似乎与实验证据一致。我们的结论是，这种新的化学-机械-生物(CMB)数学模型有可能为血管疾病的进展和治疗提供新的机械生物学见解。(C)2016年提交人。由Elsevier Ltd.出版。这是CC许可下的一篇开放获取文章
Arterial growth and remodelling (G&R) is mediated by vascular cells in response to their chemical and mechanical environment. To date, mechanical and biochemical stimuli tend to be modelled separately, however this ignores their complex interplay. Here, we present a novel mathematical model of arterial chemo-mechano-biology. We illustrate its application to the development of an inflammatory aneurysm in the descending human aorta.The arterial wall is modelled as a bilayer cylindrical non-linear elastic membrane, which is internally pressurised and axially stretched. The medial degradation that accompanies aneurysm development is driven by an inflammatory response. Collagen remodelling is simulated by adaption of the natural reference configuration of constituents; growth is simulated by changes in normalised mass-densities. We account for the distribution of attachment stretches that collagen fibres are configured to the matrix and, innovatively, allow this distribution to remodel. This enables the changing functional role of the adventitia to be simulated. Fibroblast-mediated collagen growth is represented using a biochemical pathway model: a system of coupled non-linear ODEs governs the evolution of fibroblast properties and levels of key biomolecules under the regulation of Transforming Growth Factor (TGF)-beta, a key promoter of matrix deposition.Given physiologically realistic targets, different modes of aneurysm development can be captured, while the predicted evolution of biochemical variables is qualitatively consistent with trends observed experimentally. Interestingly, we observe that increasing the levels of collagen-promoting TGF-beta results in arrest of aneurysm growth, which seems to be consistent with experimental evidence. We conclude that this novel Chemo-Mechano-Biological (CMB) mathematical model has the potential to provide new mechanobiological insight into vascular disease progression and therapy. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license