Transcriptional response of the heart to vagus nerve stimulation.

IF 2.5 4区 生物学 Q3 CELL BIOLOGY
Physiological genomics Pub Date : 2024-02-01 Epub Date: 2023-12-04 DOI:10.1152/physiolgenomics.00095.2023
Daniel O Kellett, Qadeer Aziz, Jonathan D Humphries, Alla Korsak, Alice Braga, Ana Gutierrez Del Arroyo, Marilena Crescente, Andrew Tinker, Gareth L Ackland, Alexander V Gourine
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引用次数: 0

Abstract

Heart failure is a major clinical problem, with treatments involving medication, devices, and emerging neuromodulation therapies such as vagus nerve stimulation (VNS). Considering the ongoing interest in using VNS to treat cardiovascular disease, it is important to understand the genetic and molecular changes developing in the heart in response to this form of autonomic neuromodulation. This experimental animal (rat) study investigated the immediate transcriptional response of the ventricular myocardium to selective stimulation of vagal efferent activity using an optogenetic approach. Vagal preganglionic neurons in the dorsal motor nucleus of the vagus nerve were genetically targeted to express light-sensitive chimeric channelrhodopsin variant ChIEF and stimulated using light. RNA sequencing of the left ventricular myocardium identified 294 differentially expressed genes (false discovery rate < 0.05). Qiagen Ingenuity Pathway Analysis (IPA) highlighted 118 canonical pathways that were significantly modulated by vagal activity, of which 14 had a z score of ≥2/≤-2, including EIF-2, IL-2, integrin, and NFAT-regulated cardiac hypertrophy. IPA revealed the effect of efferent vagus stimulation on protein synthesis, autophagy, fibrosis, autonomic signaling, inflammation, and hypertrophy. IPA further predicted that the identified differentially expressed genes were the targets of 50 upstream regulators, including transcription factors (e.g., MYC and NRF1) and microRNAs (e.g., miR-335-3p and miR-338-3p). These data demonstrate that the vagus nerve has a major impact on the myocardial expression of genes involved in the regulation of key biological pathways. The transcriptional response of the ventricular myocardium induced by stimulation of vagal efferents is consistent with the beneficial effect of maintained/increased vagal activity on the heart.NEW & NOTEWORTHY This experimental animal study investigated the immediate transcriptional response of the ventricular myocardium to selective stimulation of vagal efferent activity. Vagal stimulation induced significant transcriptional changes in the heart involving the pathways controlling autonomic signaling, inflammation, fibrosis, and hypertrophy. This study provides the first direct evidence that myocardial gene expression is modulated by the activity of the autonomic nervous system.

心脏对迷走神经刺激的转录反应。
心力衰竭是一个主要的临床问题,其治疗涉及药物,设备和新兴的神经调节疗法,如迷走神经刺激(VNS)。考虑到使用VNS治疗心血管疾病的持续兴趣,了解这种自主神经调节形式在心脏中发生的遗传和分子变化是很重要的。本实验动物(大鼠)研究利用光遗传学方法研究了心室心肌对迷走神经传出活动选择性刺激的即时转录反应。以迷走神经背运动核的迷走神经节前神经元为基因靶点,表达光敏感嵌合通道视紫红质变体ChIEF,并进行光刺激。左心室心肌RNA测序鉴定出294个差异表达基因(DEGs),错误发现率
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Physiological genomics
Physiological genomics 生物-生理学
CiteScore
6.10
自引率
0.00%
发文量
46
审稿时长
4-8 weeks
期刊介绍: The Physiological Genomics publishes original papers, reviews and rapid reports in a wide area of research focused on uncovering the links between genes and physiology at all levels of biological organization. Articles on topics ranging from single genes to the whole genome and their links to the physiology of humans, any model organism, organ, tissue or cell are welcome. Areas of interest include complex polygenic traits preferably of importance to human health and gene-function relationships of disease processes. Specifically, the Journal has dedicated Sections focused on genome-wide association studies (GWAS) to function, cardiovascular, renal, metabolic and neurological systems, exercise physiology, pharmacogenomics, clinical, translational and genomics for precision medicine, comparative and statistical genomics and databases. For further details on research themes covered within these Sections, please refer to the descriptions given under each Section.
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