Myocyte-fibroblast communication in cardiac fibrosis and arrhythmias: Mechanisms and model systems.
Myocyte-fibroblast communication in cardiac fibrosis and arrhythmias: Mechanisms and model systems.
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DOI：
10.1016/j.yjmcc.2016.03.005
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发表时间：
2016-05
影响因子：
5
通讯作者：
Sheikh F
中科院分区：
文献类型：
--
作者：
Pellman J;Zhang J;Sheikh F
心脏纤维化和心律失常的发展是由心脏中心肌细胞和成纤维细胞的活动和通信控制的。肌细胞-成纤维细胞相互作用通过直接和间接方式发生，包括旁分泌介质、细胞外基质相互作用、电调节器、机械连接和膜纳米管。在患病的心脏中，心肌细胞和成纤维细胞的比例和活性以及心肌细胞-成纤维细胞的相互作用发生变化，并被认为有助于疾病的进程，包括纤维化和致心律失常活动的发展。成纤维细胞在调节心肌细胞电和肥大活性方面发挥着重要作用，但有关这些相互作用的知识仍然存在差距。该领域的研究需要开发独特的方法来分离和控制肌细胞-成纤维细胞的相互作用。已经开发了许多用于 2D 和 3D 共培养系统的方法，而该领域越来越多的部分是使用更好的工具用于体内系统，包括心肌细胞和成纤维细胞特异性 Cre 小鼠系，用于细胞类型特异性基因消融。本综述将重点关注 (i) 肌细胞-成纤维细胞通讯机制及其对心脏纤维化和心律失常等疾病特征的影响，以及 (ii) 该领域正在使用和目前开发的方法。
Development of cardiac fibrosis and arrhythmias is controlled by the activity of and communication between cardiomyocytes and fibroblasts in the heart. Myocyte-fibroblast interactions occur via both direct and indirect means including paracrine mediators, extracellular matrix interactions, electrical modulators, mechanical junctions, and membrane nanotubes. In the diseased heart, cardiomyocyte and fibroblast ratios and activity, and thus myocyte-fibroblast interactions, change and are thought to contribute to the course of disease including development of fibrosis and arrhythmogenic activity. Fibroblasts have a developing role in modulating cardiomyocyte electrical and hypertrophic activity, however gaps in knowledge regarding these interactions still exist. Research in this field has necessitated the development of unique approaches to isolate and control myocyte-fibroblast interactions. Numerous methods for 2D and 3D co-culture systems have been developed, while a growing part of this field is in the use of better tools for in vivo systems including cardiomyocyte and fibroblast specific Cre mouse lines for cell type specific genetic ablation. This review will focus on (i) mechanisms of myocyte-fibroblast communication and their effects on disease features such as cardiac fibrosis and arrhythmias as well as (ii) methods being used and currently developed in this field.