Tissue-level biomechanical properties and function derive from underlying cell signaling, which regulates mass deposition, organization, and removal. Here, we couple two existing modeling frameworks to capture associated multiscale interactions—one for vessel-level growth and remodeling and one for cell-level signaling—and illustrate utility by simulating aortic remodeling. At the vessel level, we employ a constrained mixture model describing turnover of individual wall constituents (elastin, intramural cells, and collagen), which has proven useful in predicting diverse adaptations as well as disease progression using phenomenological constitutive relations. Nevertheless, we now seek an improved mechanistic understanding of these processes; we replace phenomenological relations in the mixture model with a logic-based signaling model, which yields a system of ordinary differential equations predicting changes in collagen synthesis, matrix metalloproteinases, and cell proliferation in response to altered intramural stress, wall shear stress, and exogenous angiotensin II. This coupled approach promises improved understanding of the role of cell signaling in achieving tissue homeostasis and allows us to model feedback between vessel mechanics and cell signaling. We verify our model predictions against data from the hypertensive murine infrarenal abdominal aorta as well as results from validated phenomenological models, and consider effects of noisy signaling and heterogeneous cell populations.

组织水平的生物力学特性和功能源自潜在的细胞信号传导，它调节物质沉积、组织和去除。在这里，我们结合了两个现有的建模框架来捕获相关的多尺度相互作用——一个用于血管水平的生长和重塑，一个用于细胞水平的信号传导——并通过模拟主动脉重塑来说明实用性。在血管水平，我们采用了一个受约束的混合模型来描述单个壁成分（弹性蛋白、壁内细胞和胶原蛋白）的周转，这已被证明可用于使用现象学本构关系预测各种适应和疾病进展。尽管如此，我们现在寻求对这些过程的更好的机械理解；我们用基于逻辑的信号模型替换混合模型中的现象学关系，这产生了一个常微分方程系统，可预测胶原合成、基质金属蛋白酶和细胞增殖对改变的壁内应力、壁剪切应力和外源性血管紧张素 II 的反应。这种耦合方法有望提高对细胞信号传导在实现组织稳态中的作用的理解，并使我们能够模拟血管力学和细胞信号传导之间的反馈。我们根据来自高血压鼠肾下腹主动脉的数据以及经过验证的现象学模型的结果验证我们的模型预测，并考虑噪声信号和异质细胞群的影响。壁剪切应力和外源性血管紧张素 II。这种耦合方法有望提高对细胞信号传导在实现组织稳态中的作用的理解，并使我们能够模拟血管力学和细胞信号传导之间的反馈。我们根据来自高血压鼠肾下腹主动脉的数据以及经过验证的现象学模型的结果验证我们的模型预测，并考虑噪声信号和异质细胞群的影响。壁剪切应力和外源性血管紧张素 II。这种耦合方法有望提高对细胞信号传导在实现组织稳态中的作用的理解，并使我们能够模拟血管力学和细胞信号传导之间的反馈。我们根据来自高血压鼠肾下腹主动脉的数据以及经过验证的现象学模型的结果验证我们的模型预测，并考虑噪声信号和异质细胞群的影响。