Abstract：
In the Ross procedure, a patient\'s pulmonary valve is transplanted in the aortic position. Despite advantages of this surgery, reoperation is still needed in many cases due to excessive dilatation of the pulmonary autograft. To further understand the failure mechanisms, we propose a multiscale model predicting adaptive processes in the autograft at the cell and tissue scale. The cell-scale model consists of a network model, that includes important signaling pathways and relations between relevant transcription factors and their target genes. The resulting gene activity leads to changes in the mechanical properties of the tissue, modeled as a constrained mixture of collagen, elastin and smooth muscle. The multiscale model is calibrated with findings from experiments in which seven sheep underwent the Ross procedure. The model is then validated against a different set of sheep experiments, for which a qualitative agreement between model and experiment is found. Model outcomes at the cell scale, including the activity of genes and transcription factors, also match experimentally obtained transcriptomics data.
摘要：
在罗斯程序中,患者的肺动脉瓣在主动脉位置移植。尽管这种手术有优势，由于肺自体移植物过度扩张，在许多情况下仍需要再次手术。为了进一步理解故障机制，我们提出了一个多尺度模型，在细胞和组织尺度上预测自体移植物的自适应过程。细胞尺度模型由网络模型组成，其中包括重要的信号通路以及相关转录因子与其靶基因之间的关系。由此产生的基因活性导致组织机械特性的变化，建模为胶原蛋白的约束混合物，弹性蛋白和平滑肌。多尺度模型是根据实验结果校准的，其中七只绵羊接受了Ross程序。然后针对一组不同的绵羊实验对模型进行验证，为此，在模型和实验之间找到了定性的一致性。在细胞尺度上模拟结果，包括基因和转录因子的活性，也匹配实验获得的转录组学数据。
