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首页> 外文期刊>Cellular Signalling >Rate and irregularity of electrical activation during atrial fibrillation affect myocardial NGF expression via different signalling routes
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Rate and irregularity of electrical activation during atrial fibrillation affect myocardial NGF expression via different signalling routes

机译：心房颤动期间电激活的速率和不规则性通过不同的信号传导途径影响心肌NGF的表达

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摘要

An irregular ventricular response during atrial fibrillation (AF) has been shown to mediate an increase in sympathetic nerve activity in human subjects. The molecular mechanisms remain unclear. This study aimed to investigate the impact of rate and irregularity on nerve growth factor (NGF) expression in cardiomyocytes, since NGF is known to be the main contributor to cardiac sympathetic innervation density. Cell cultures of neonatal rat ventricular myocytes were electrically stimulated for 48. h with increasing rates (0, 5 and 50. Hz) and irregularity (standard deviation (SD) = 5%, 25% and 50% of mean cycle length). Furthermore, we analyzed the calcineurin-NFAT and the endothelin-1 signalling pathways as possible contributors to NGF regulation during arrhythmic stimulation. We found that the increase of NGF expression reached its maximum at the irregularity of 25% SD by 5. Hz (NGF: 5. Hz 0% SD = 1 vs. 5. Hz 25% SD = 1.57, P<0.05). Specific blockade of the ET-A receptor by BQ123 could abolish this NGF increase (NGF: 5. Hz 25% SD. +. BQ123 = 0.66, P<0.05). High frequency electrical field stimulation (HFES) with 50. Hz decreased the NGF expression in a significant manner (NGF: 50. Hz = 0.55, P<0.05). Inhibition of calcineurin-NFAT signalling with cyclosporine-A or 11R-VIVIT abolished the HFES induced NGF down-regulation (NGF: 50. Hz. +. CsA = 1.14, P<0.05). In summary, this study reveals different signalling routes of NGF expression in cardiomyocytes exposed to increasing rates and irregularity. Whether this translates into different degrees of NGF expression and possibly neural sympathetic growth in various forms of ventricular rate control during AF remains to be elucidated in further studies.
机译：房颤（AF）期间不规则的心室反应已显示出介导人类受试者交感神经活动增加。分子机制仍不清楚。这项研究旨在调查速率和不规则性对心肌细胞中神经生长因子（NGF）表达的影响，因为已知NGF是导致心脏交感神经支配密度的主要因素。电刺激新生大鼠心室肌细胞的细胞培养48 h，速率（0、5和50 Hz）和不规则性增加（标准偏差（SD）=平均周期长度的5％，25％和50％）。此外，我们分析了钙调神经磷酸酶-NFAT和内皮素-1信号通路可能是心律失常刺激过程中对NGF调节的可能贡献者。我们发现，NGF表达的增加在25％SD的不规则性处增加了5. Hz（NGF：5。Hz 0％SD = 1与5. Hz 25％SD = 1.57，P <0.05）。 BQ123对ET-A受体的特异性阻断可以消除​​这种NGF的增加（NGF：5。Hz 25％SD。+。BQ123 = 0.66，P <0.05）。 50. Hz的高频电场刺激（HFES）显着降低了NGF的表达（NGF：50。Hz = 0.55，P <0.05）。用环孢霉素-A或11R-VIVIT抑制钙调神经磷酸酶-NFAT信号消除了HFES诱导的NGF下调（NGF：50.Hz。+。CsA ＝ 1.14，P ＜0.05）。总之，这项研究揭示了暴露于增加的速率和不规则性的心肌细胞中NGF表达的不同信号传导途径。在AF期间，这是否转化为不同程度的NGF表达以及在各种形式的心室率控制中是否可能发生神经交感生长仍有待进一步研究。

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