Evidence map›Paper›PMID 39071113›Full record

ArticlePhysiological genomics2024

Transcriptional response of the heart to vagus nerve stimulation.

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

Abstract read
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In one paragraph

Article in Physiological genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Daniel O KellettCentre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
Qadeer AzizCentre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
Jonathan D HumphriesDepartment of Life Sciences, Manchester Metropolitan University, Manchester, UK.
Alla KorsakCentre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
Alice BragaCentre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
Ana Gutierrez Del ArroyoCentre for Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Queen Mary University of London, London, UK.
Marilena CrescenteDepartment of Life Sciences, Manchester Metropolitan University, Manchester, UK.
Andrew TinkerCentre for Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Queen Mary University of London, London, UK.
Gareth L AcklandTranslational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK.
Alexander V GourineCentre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.

Funding

British Heart Foundation
6 · The paper itself

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.

Indexed as

Vagus NerveVagus Nerve StimulationAnimalsGene Expression ProfilingGene Expression RegulationHeartMaleMyocardiumOptogeneticsRatsRats, Sprague-DawleyTranscription, Geneticautonomic nervous systemheartRNA sequencingtranscriptomevagus nerve.

Identifiers

PMID39071113
PMCPMC7616044

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.