ArticleJournal of molecular and cellular cardiology2014
Connexin40 abnormalities and atrial fibrillation in the human heart.
Article in Journal of molecular and cellular cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- Guideline
- 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.Journal of the American College of Cardiology · 2024Guideline
- Resistance to atrial fibrillation domestication and mitochondrial dysfunction in sheep: a potential key role of the TCA cycle and mitochondrial redox state.Redox biology · 2026Article
- Murine ADAM15 Deficiency Is Associated With Atrial Remodelling and Atrial Arrhythmia Susceptibility.European journal of clinical investigation · 2026Article
- The clinical pathophysiology of atrial fibrillation: outstanding questions from bedside to bench and back.Physiological reviews · 2026Review
- Review
- Connexin 40 in atrial fibrillation: pathophysiological roles and regulatory mechanisms.Annals of medicine · 2025Review
- EXPRESSION OF CONNEXIN-40 AND INTERLEUKIN 6 GENES IN PATIENTS WITH ATRIAL FIBRILLATION.Acta clinica Croatica · 2025Article
- Sex Differences in Electrophysiology and Calcium Handling in Atrial Health and Fibrillation.Annual review of physiology · 2025Review
- Atrial Cardiomyopathy-associated Arrhythmia and the Impact of Sirtuin Signaling Pathway: A Narrative Review.Current vascular pharmacology · 2025Review
- Oxidative stress and atrial fibrillation.Journal of molecular and cellular cardiology · 2024Review
- Immune response caused by M1 macrophages elicits atrial fibrillation-like phenotypes in coculture model with isogenic hiPSC-derived cardiomyocytes.Stem cell research & therapy · 2024Article
- P2X7 receptor inhibition prevents atrial fibrillation in rodent models of depression.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Article
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
- Cohesin: an emerging master regulator at the heart of cardiac development.Molecular biology of the cell · 2023Article
- Nernst-Planck-Gaussian modelling of electrodiffusional recovery from ephaptic excitation between mammalian cardiomyocytes.Frontiers in physiology · 2023Article
- ROCK (RhoA/Rho Kinase) Activation in Atrial Fibrillation: Molecular Pathways and Clinical Implications.Current cardiology reviews · 2023Article
- A New Hope: Sodium-Glucose Cotransporter-2 Inhibition to Prevent Atrial Fibrillation.Journal of cardiovascular development and disease · 2022Review
- Atrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation.JCI insight · 2022Article
- Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Normal atrial conduction requires similar abundances and homogeneous/overlapping distributions of two connexins (Cx40 and Cx43). The remodeling of myocyte connections and altered electrical conduction associated with atrial fibrillation (AF) likely involves perturbations of these connexins. We conducted a comprehensive series of experiments to examine the abundances and distributions of Cx40 and Cx43 in the atria of AF patients. Atrial appendage tissues were obtained from patients with lone AF (paroxysmal or chronic) or normal controls. Connexins were localized by double label immunofluorescence confocal microscopy, and their overlap was quantified. Connexin proteins and mRNAs were quantified by immunoblotting and qRT-PCR. PCR amplified genomic DNA was sequenced to screen for connexin gene mutations or polymorphisms. Immunoblotting showed reductions of Cx40 protein (to 77% or 49% of control values in samples from patients with paroxysmal and chronic AF, respectively), but no significant changes of Cx43 protein levels in samples from AF patients. The extent of Cx43 immunostaining and its distribution relative to N-cadherin were preserved in the AF patient samples. Although there was variability of Cx40 staining among paroxysmal AF patients, all had some fields with substantial Cx40 heterogeneity and reduced overlap with Cx43. Cx40 immunostaining was severely reduced in all chronic AF patients. qRT-PCR showed no change in Cx43 mRNA levels, but reductions in total Cx40 mRNA (to <50%) and Cx40 transcripts A (to ~50%) and B (to <25%) as compared to controls. No Cx40 coding region mutations were identified. The frequency of promoter polymorphisms did not differ between AF patient samples and controls. Our data suggest that reduced Cx40 levels and heterogeneity of its distribution (relative to Cx43) are common in AF. Multiple mechanisms likely lead to reductions of functional Cx40 in atrial gap junctions and contribute to the pathogenesis of AF in different patients.
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Registered trials
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 OpenQuestion graph.