Cardiac fibrosis and arrhythmogenesis: the road to repair is paved with perils.
Cardiac fibrosis and arrhythmogenesis: the road to repair is paved with perils.
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DOI：
10.1016/j.yjmcc.2013.10.018
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发表时间：
2014-05
影响因子：
5
通讯作者：
Weiss, James N.
中科院分区：
文献类型：
--
作者：
Nguyen, Thao P.;Qu, Zhilin;Weiss, James N.
在健康的心脏中，心肌细胞形成电合胞体，嵌入支持性的富含成纤维细胞的细胞外基质中，该细胞外基质被设计为优化机电耦合以使心脏泵的收缩效率最大化。然而，在受伤的心脏中，成纤维细胞被激活并分化成肌成纤维细胞，其增殖并产生纤维化作为伤口愈合反应的组成部分。这篇综述讨论了成纤维细胞和纤维化，而必不可少的损伤后保持心脏壁的结构完整性，有不良的电生理效应，破坏心脏组织的正常电连接，增加心律失常的脆弱性。我们强调纤维化在改变源-汇关系以创建脆弱基质方面的双重贡献，同时促进触发因素的出现，如后去极化诱导的室性早搏复合物-这两种因素协同结合以促进折返的启动。我们还讨论了成纤维细胞和肌成纤维细胞在直接改变肌细胞电生理学中的潜在作用。深入了解这些过程可能会开辟新的治疗策略，用于预防和治疗心脏病背景下的心律失常，以及避免基于细胞的心脏再生治疗的潜在致心律失常后果。这篇文章是题为“肌细胞成纤维细胞信号在心肌病”的特刊的一部分。
In the healthy heart, cardiac myocytes form an electrical syncytium, embedded in a supportive fibroblast-rich extracellular matrix designed to optimize electromechanical coupling for maximal contractile efficiency of the heart pump. In the injured heart, however, fibroblasts are activated and differentiate into myofibroblasts that proliferate and generate fibrosis as a component of the wound-healing response. This review discusses how fibroblasts and fibrosis, while essential for maintaining the structural integrity of the heart wall after injury, have undesirable electrophysiological effects by disrupting the normal electrical connectivity of cardiac tissue to increase the vulnerability to arrhythmias. We emphasize the dual contribution of fibrosis in altering source-sink relationships to create a vulnerable substrate while simultaneously facilitating the emergence of triggers such as afterdepolarization-induced premature ventricular complexes– both factors combining synergistically to promote initiation of reentry. We also discuss the potential role of fibroblasts and myofibroblasts in directly altering myocyte electrophysiology in a pro-arrhythmic fashion. Insight into these processes may open up novel therapeutic strategies for preventing and treating arrhythmias in the setting of heart disease as well as avoiding potential arrhythmogenic consequences of cell-based cardiac regeneration therapy. This article is part of a Special Issue entitled “Myocyte-Fibroblast Signaling in Myocardium.”
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影响因子：
24
作者：
Mewton, Nathan;Liu, Chia Ying;Croisille, Pierre;Bluemke, David;Lima, Joao A. C.
通讯作者：
Lima, Joao A. C.
膜纳米管介导的心肌细胞和心成纤维细胞之间的长距离细胞间连接
影响因子：
10.8
作者：
He, Kangmin;Shi, Xiaoli;Zhang, Youyi
通讯作者：
Zhang, Youyi
DOI：
10.1152/ajpheart.00079.2007
发表时间：
2007-08-01
影响因子：
4.8
作者：
Akar, Fadi G.;Nass, Robert D.;Tomaselli, Gordon F.
通讯作者：
Tomaselli, Gordon F.
影响因子：
20.1
作者：
Gaudesius, G;Miragoli, M;Rohr, S
通讯作者：
Rohr, S
影响因子：
5.5
作者：
Duffy, Heather S.
通讯作者：
Duffy, Heather S.