Atrial remodeling, fibrosis, and atrial fibrillation.
Atrial remodeling, fibrosis, and atrial fibrillation.
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DOI：
10.1016/j.tcm.2014.12.015
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发表时间：
2015-08
影响因子：
9.3
通讯作者：
Kaur K
中科院分区：
文献类型：
--
作者：
Jalife J;Kaur K
房颤（AF）是临床实践中最常见的心律失常，其长期存在的基本机制尚不清楚，这在一定程度上解释了为什么房颤的预防和治疗仍然不够理想。虽然一些临床参数已被确定为预测某些患者从阵发性房颤到持续性房颤的转变，但导致这种进展的分子、电生理和结构变化尚未得到详细描述。氧化应激、心房扩张、钙超载、炎症、microrna和肌成纤维细胞活化都被认为与af诱导的心房重构有关。然而，尚不清楚这种改变在多大程度上以及在哪个时间点影响房颤的重塑过程。在这里，我们假设了一个全面的模型，可能为未来研究房颤的持久机制开辟新的途径。我们从一个前提开始，即AF永久化的进展是具有不同动力学的多种信号通路相互作用的结果。其中一些途径具有较快的动力学（如氧化应激介导的不应期缩短）；其他可能依赖于动力学较慢的分子过程（例如，通过炎症和成纤维细胞激活介导的肌细胞离子通道蛋白表达的转录变化）。我们强调，需要充分了解这些途径之间的关系，才能找到新的、真正有效的AF治疗和预防靶点。
Fundamental mechanisms governing the perpetuation of atrial fibrillation (AF), the most common arrhythmia seen in clinical practice, are poorly understood, which explains in part why AF prevention and treatment remain suboptimal. Although some clinical parameters have been identified as predicting a transition from paroxysmal to persistent AF in some patients, the molecular, electrophysiological and structural changes leading to such a progression have not been described in detail. Oxidative stress, atrial dilatation, calcium overload, inflammation, microRNAs and myofibroblast activation are all thought to be involved in AF-induced atrial remodeling. However, it is unknown to what extent and at which time points such alterations influence the remodeling process that perpetuates AF. Here we postulate a comprehensive model that might open new pathways for future investigation into mechanisms of AF perpetuation. We start from the premise that the progression to AF perpetuation is the result of an interplay among manifold signaling pathways with differing kinetics. Some such pathways have relatively fast kinetics (e.g., oxidative stress mediated shortening of refractory period); others likely depend on molecular processes with slower kinetics (e.g., transcriptional changes in myocyte ion channel protein expression mediated through inflammation and fibroblast activation). We stress the need to fully understand the relationships among such pathways should one hope to identify novel, truly effective targets for AF therapy and prevention.
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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：
3
作者：
Baum J;Duffy HS
通讯作者：
Duffy HS
影响因子：
20.1
作者：
Du J;Xie J;Zhang Z;Tsujikawa H;Fusco D;Silverman D;Liang B;Yue L
通讯作者：
Yue L
影响因子：
20.1
作者：
Andrade, Jason;Khairy, Paul;Nattel, Stanley
通讯作者：
Nattel, Stanley
影响因子：
10.8
作者：
Driesen, RB;Dispersyn, GD;Ramaekers, FCS
通讯作者：
Ramaekers, FCS