Evidence map›Paper›PMID 39189070›Full record

ArticleDisease models & mechanisms2024

Reduced connexin-43 expression, slow conduction and repolarisation dispersion in a model of hypertrophic cardiomyopathy.

Seakcheng Lim, Melissa M Mangala, Mira Holliday, Henrietta Cserne Szappanos, Samantha Barratt-Ross, Serena Li, Jordan Thorpe, Whitney Liang, Ginell N Ranpura, Jamie I Vandenberg and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Disease models & mechanisms, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Atrial electrophysiology in hypertrophic cardiomyopathy: current insights and knowledge gaps.Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2026
    Review
  2. Review
  3. Article
  4. Research progress of connexin 43 in cardiovascular diseases.Frontiers in cardiovascular medicine · 2025
    Review
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

13 authors.

Seakcheng LimAgnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney 2050, Australia.
Melissa M MangalaVictor Chang Cardiac Research Institute, Sydney, 2010, Australia.
Mira HollidayAgnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney 2050, Australia.
Henrietta Cserne SzappanosSchool of Human Sciences, The University of Western Australia, Crawley 6009, Australia.
Samantha Barratt-RossAgnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney 2050, Australia.
Serena LiAgnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney 2050, Australia.
Jordan ThorpeVictor Chang Cardiac Research Institute, Sydney, 2010, Australia.
Whitney LiangVictor Chang Cardiac Research Institute, Sydney, 2010, Australia.
Ginell N RanpuraAgnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney 2050, Australia.
Jamie I VandenbergVictor Chang Cardiac Research Institute, Sydney, 2010, Australia.ORCID 0000-0002-3859-3716
Christopher SemsarianAgnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney 2050, Australia.
Adam P HillORCID 0000-0002-6403-1282
Livia C HoolVictor Chang Cardiac Research Institute, Sydney, 2010, Australia.

Funding

National Health and Medical Research Council APP1143321NSW HealthUNSW SydneyWoodside Energy
6 · The paper itself

Abstract

Hypertrophic cardiomyopathy (HCM) is an inherited heart muscle disease that is characterised by left ventricular wall thickening, cardiomyocyte disarray and fibrosis, and is associated with arrhythmias, heart failure and sudden death. However, it is unclear to what extent the electrophysiological disturbances that lead to sudden death occur secondary to structural changes in the myocardium or as a result of HCM cardiomyocyte electrophysiology. In this study, we used an induced pluripotent stem cell model of the R403Q variant in myosin heavy chain 7 (MYH7) to study the electrophysiology of HCM cardiomyocytes in electrically coupled syncytia, revealing significant conduction slowing and increased spatial dispersion of repolarisation - both well-established substrates for arrhythmia. Analysis of rhythmonome protein expression in MYH7 R403Q cardiomyocytes showed reduced expression of connexin-43 (also known as GJA1), sodium channels and inward rectifier potassium channels - a three-way hit that reduces electrotonic coupling and slows cardiac conduction. Our data represent a previously unreported, biophysical basis for arrhythmia in HCM that is intrinsic to cardiomyocyte electrophysiology. Later in the progression of the disease, these proarrhythmic phenotypes may be accentuated by myocyte disarray and fibrosis to contribute to sudden death.

Indexed as

Cardiomyopathy, HypertrophicConnexin 43Heart Conduction SystemMyocytes, CardiacMyosin Heavy ChainsAction PotentialsArrhythmias, CardiacCardiac MyosinsGiant CellsHumansInduced Pluripotent Stem CellsCardiac MyosinsConnexin 43MYH7 protein, humanMyosin Heavy ChainsArrhythmiaCardiovascular diseaseElectrophysiologyStem cells

Identifiers

PMID39189070
PMCPMC11381919

What OpenQuestion 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 OpenQuestion graph.