Computational Approaches to Understanding the Role of Fibroblast-Myocyte Interactions in Cardiac Arrhythmogenesis.
Computational Approaches to Understanding the Role of Fibroblast-Myocyte Interactions in Cardiac Arrhythmogenesis.
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DOI：
10.1155/2015/465714
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发表时间：
2015
影响因子：
--
通讯作者：
Christini DJ
中科院分区：
文献类型：
--
作者：
Brown TR;Krogh-Madsen T;Christini DJ
成人心脏由心肌细胞密集网络构成，周围是非心肌细胞，其中数量最多的是心脏成纤维细胞。几种心脏疾病，如心肌梗死或扩张型心肌病，都与成纤维细胞密度增加（即纤维化）有关。成纤维细胞在心脏电和机械功能障碍的发展中起着重要作用；然而，其潜在机制仅被部分了解。一种被广泛研究的机制表明，成纤维细胞产生过量的细胞外基质，导致胶原隔。这些胶原隔减缓传导，造成曲折传导路径，并使心肌细胞解偶联，从而形成心律失常的基质。另一种新兴机制表明，成纤维细胞通过缝隙连接与心肌细胞直接电相互作用促进心律失常发生。由于在天然心脏组织中研究成纤维细胞 - 心肌细胞偶联存在困难，计算模型和体外实验促进了对成纤维细胞介导的心肌细胞动作电位形态、传导速度、自发兴奋性和折返易感性变化的潜在机制的研究。在本文中，我们总结了现有计算研究的主要发现，这些研究探讨了成纤维细胞 - 心肌细胞相互作用在正常和患病心脏中的影响。然后，我们介绍了我们小组对电压依赖性缝隙连接在成纤维细胞 - 心肌细胞相互作用中的潜在作用的研究。
The adult heart is composed of a dense network of cardiomyocytes surrounded by nonmyocytes, the most abundant of which are cardiac fibroblasts. Several cardiac diseases, such as myocardial infarction or dilated cardiomyopathy, are associated with an increased density of fibroblasts, that is, fibrosis. Fibroblasts play a significant role in the development of electrical and mechanical dysfunction of the heart; however the underlying mechanisms are only partially understood. One widely studied mechanism suggests that fibroblasts produce excess extracellular matrix, resulting in collagenous septa. These collagenous septa slow propagation, cause zig-zag conduction paths, and decouple cardiomyocytes resulting in a substrate for arrhythmia. Another emerging mechanism suggests that fibroblasts promote arrhythmogenesis through direct electrical interactions with cardiomyocytes via gap junctions. Due to the challenges of investigating fibroblast-myocyte coupling in native cardiac tissue, computational modeling and in vitro experiments have facilitated the investigation into the mechanisms underlying fibroblast-mediated changes in cardiomyocyte action potential morphology, conduction velocity, spontaneous excitability, and vulnerability to reentry. In this paper, we summarize the major findings of the existing computational studies investigating the implications of fibroblast-myocyte interactions in the normal and diseased heart. We then present investigations from our group into the potential role of voltage-dependent gap junctions in fibroblast-myocyte interactions.