Evidence map›Paper›PMID 40265247›Full record

ArticleCirculation. Arrhythmia and electrophysiology2025

Heart Rate Mystery Unveiled: Sex Differences in Human Sinoatrial Node Genes and Female Tachycardia.

Ning Li, Amy Webb, James Kennelly, Roshan Sharma, Bryan A Whitson, Peter J Mohler, John D Hummel, Jichao Zhao, Vadim V Fedorov

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation. Arrhythmia and electrophysiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Ning LiDepartment of Physiology and Cell Biology (N.L., P.J.M., V.V.F.), The Ohio State University College of Medicine Wexner Medical Center, Columbus.
Amy WebbDepartment of Biomedical Informatics (A.W.), The Ohio State University College of Medicine Wexner Medical Center, Columbus.
James KennellyAuckland Bioengineering Institute, The University of Auckland, New Zealand (J.K., R.S., J.Z.).ORCID 0000-0002-7631-5426
Roshan SharmaAuckland Bioengineering Institute, The University of Auckland, New Zealand (J.K., R.S., J.Z.).
Bryan A WhitsonDepartment of Surgery, Division of Cardiac Surgery (B.A.W.), The Ohio State University College of Medicine Wexner Medical Center, Columbus.ORCID 0000-0003-0040-3638
Peter J MohlerDepartment of Physiology and Cell Biology (N.L., P.J.M., V.V.F.), The Ohio State University College of Medicine Wexner Medical Center, Columbus.ORCID 0000-0002-7977-8717
John D HummelBob and Corrine Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute (N.L., P.J.M., J.D.H., V.V.F.), The Ohio State University College of Medicine Wexner Medical Center, Columbus.ORCID 0000-0002-2629-2553
Jichao ZhaoAuckland Bioengineering Institute, The University of Auckland, New Zealand (J.K., R.S., J.Z.).ORCID 0000-0003-3303-0401
Vadim V FedorovDepartment of Physiology and Cell Biology (N.L., P.J.M., V.V.F.), The Ohio State University College of Medicine Wexner Medical Center, Columbus.ORCID 0000-0003-1035-4569

Funding

Targeting the Arrhythmogenic Sources of Human Atrial FibrillationR01HL135109 · NHLBI · OHIO STATE UNIVERSITY · PI Vadim V Fedorov · 2017 to 2026
$6.0M
Integration of structure and signaling in cardiac pacemaker functionR01HL115580 · NHLBI · OHIO STATE UNIVERSITY · PI FEDOROV, VADIM V · 2013 to 2021
$4.2M
NHLBI NIH HHS R01 HL115580NHLBI NIH HHS R01 HL135109
6 · The paper itself

Abstract

backgroundDespite over a century of clinical electrocardiographic studies showing that women exhibit a faster resting heart rate (HR), the mechanisms underlying sex differences in HR remain unresolved. Moreover, inappropriate sinus tachycardia primarily affects women, whereas men are at a higher risk for conduction block and atrial fibrillation. We hypothesized that the sexual dimorphism of genes responsible for sinoatrial node (SAN) pacemaking and signaling pathways may contribute to the sex differences in HR and susceptibility to arrhythmias.

methodsHuman SAN central pacemaker and right atrial tissue were isolated from nondiseased ex vivo donor hearts. Gene expressions were quantified and validated using the transcriptomic panel and quantitative polymerase chain reaction. Gene set enrichment analysis, Ingenuity Pathway Analysis, and human-specific SAN models were utilized to define regulatory mechanisms and functional impacts of sex-biased gene transcription.

resultsWe identified differentially expressed region- and sex-specific genes, with gene sets enriched in HR regulation (eg,

conclusionsThe human SAN exhibits region-specific sexual dimorphism in pacemaking gene sets. Higher expression of

Indexed as

Heart RateSinoatrial NodeTachycardia, SinusAction PotentialsAdultAgedFemaleGene Expression ProfilingGene Expression RegulationHumansHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMaleMiddle AgedSex FactorsT-Box Domain ProteinsTranscriptomeHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsT-Box Domain ProteinsTBX3 protein, humanatrial fibrillationestradiolheart rateinflammationsex characteristicssinoatrial nodesinus tachycardia

Identifiers

PMID40265247
PMCPMC12416543

What Socratic holds

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Registered trials

None linked

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.