Transcriptional response of the heart to vagus nerve stimulation.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-02-01 Epub Date: 2023-12-04 DOI:10.6084/m9.figshare.24449590
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 left ventricular myocardium identified 294 differentially expressed genes (DEGs, 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 signalling, inflammation, and hypertrophy. IPA further predicted that the identified DEGs were the targets of 50 upstream regulators, including transcription factors (e.g., MYC, NRF1) and microRNAs (e.g., miR-335-3p, miR-338-3p). These data demonstrate that the vagus nerve has a major impact on myocardial expression of genes involved in 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.

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,治疗方法包括药物、器械和新兴的神经调控疗法,如迷走神经刺激(VNS)。考虑到目前人们对使用迷走神经刺激治疗心血管疾病的兴趣,了解心脏对这种形式的自律神经调节所产生的基因和分子变化非常重要。这项动物实验(大鼠)研究采用光遗传学方法调查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。迷走神经背侧运动核中的迷走神经节前神经元通过基因定向表达光敏嵌合通道荧光素变体 ChIEF,并使用光进行刺激。左心室心肌的 RNA 测序发现了 294 个差异表达基因(DEGs,误发现率为 0.5%)。
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
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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