Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology.
Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology.
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DOI：
10.3390/cells10112852
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发表时间：
2021-10-22
期刊：
影响因子：
6
通讯作者：
Loewe A
中科院分区：
文献类型：
--
作者：
Sánchez J;Trenor B;Saiz J;Dössel O;Loewe A
心房颤动时，心脏组织从分子水平到组织水平经历不同尺度的重构过程。肌成纤维细胞是一个对电和结构重塑都有贡献的核心参与者。基于最近关于肌成纤维细胞收缩能力的实验证据，我们扩展了具有Ca 2+处理组件的生物物理肌成纤维细胞模型，并研究了对细胞和组织电生理学的影响。使用遗传算法，我们拟合的肌成纤维细胞模型参数，现有的体外数据。计算机模拟实验表明，Ca 2+电流可以解释实验观察到的肌成纤维细胞静息膜电位的变异性。L-型钙电流的存在下，可以触发automaticity在肌成纤维细胞的周期长度为799.9毫秒。肌细胞动作电位延长时，再加上肌成纤维细胞与Ca 2+处理机械。不同的空间肌成纤维细胞分布模式将诱发心律失常的易损窗口从非纤维化组织的12 ms增加到22 ± 2.5 ms，并改变了折返动力学。我们的研究结果表明，Ca 2+处理可以显着影响肌成纤维细胞电生理学和改变心房组织的肌细胞与肌成纤维细胞耦合组成的电传播。这些发现可以为实验验证实验提供信息，以进一步阐明肌成纤维细胞Ca 2+处理在心房肌发生中的作用。
During atrial fibrillation, cardiac tissue undergoes different remodeling processes at different scales from the molecular level to the tissue level. One central player that contributes to both electrical and structural remodeling is the myofibroblast. Based on recent experimental evidence on myofibroblasts’ ability to contract, we extended a biophysical myofibroblast model with Ca2+ handling components and studied the effect on cellular and tissue electrophysiology. Using genetic algorithms, we fitted the myofibroblast model parameters to the existing in vitro data. In silico experiments showed that Ca2+ currents can explain the experimentally observed variability regarding the myofibroblast resting membrane potential. The presence of an L-type Ca2+ current can trigger automaticity in the myofibroblast with a cycle length of 799.9 ms. Myocyte action potentials were prolonged when coupled to myofibroblasts with Ca2+ handling machinery. Different spatial myofibroblast distribution patterns increased the vulnerable window to induce arrhythmia from 12 ms in non-fibrotic tissue to 22 ± 2.5 ms and altered the reentry dynamics. Our findings suggest that Ca2+ handling can considerably affect myofibroblast electrophysiology and alter the electrical propagation in atrial tissue composed of myocytes coupled with myofibroblasts. These findings can inform experimental validation experiments to further elucidate the role of myofibroblast Ca2+ handling in atrial arrhythmogenesis.
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影响因子：
5
作者：
Adapala RK;Thoppil RJ;Luther DJ;Paruchuri S;Meszaros JG;Chilian WM;Thodeti CK
通讯作者：
Thodeti CK
影响因子：
10.8
作者：
Camelliti, P;Devlin, GP;Green, CR
通讯作者：
Green, CR
DOI：
10.1152/ajpheart.00878.2012
发表时间：
2013-05-01
影响因子：
4.8
作者：
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通讯作者：
Morley, Gregory E.
影响因子：
4.6
作者：
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通讯作者：
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影响因子：
5.5
作者：
Chatelier, Aurelien;Mercier, Aurelie;Faivre, Jean Francois
通讯作者：
Faivre, Jean Francois