Evidence map›Paper›PMID 42569976›Full record

ArticleJACC. Clinical electrophysiology2026

LMNA Deficiency Reveals a Role for SK3 Channel Dysfunction in Atrioventricular Block.

Tingting Li, Xiaolei Wang, Jia Song, Anna K Shinohara, Luge Li, Adeniyi Gbenga Adeleye, William Whitfield, Yaqueline Esperanza Gutierrez, Yue Yuan, Min Zhang and 3 more

Abstract read
In one paragraph

Article in JACC. Clinical electrophysiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

13 authors.

Tingting LiSection of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Xiaolei WangSection of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Jia SongSection of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Anna K ShinoharaSection of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Luge LiSection of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Adeniyi Gbenga AdeleyeSection of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
William WhitfieldSection of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Yaqueline Esperanza GutierrezSection of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Yue YuanSection of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Min ZhangPediatric Translational Medicine Institute and Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Bradley K McConnellPharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas, USA.
Na LiSection of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas, USA. Electronic address: nal@bcm.edu.
Mihail G CheluCardiovascular Research Institute, Baylor College of Medicine, Houston, Texas, USA; Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA; Texas Heart Institute at Baylor College of Medicine and Baylor St. Luke's Medical Center, Houston, Texas, USA. Electronic address: mihail.chelu@bcm.edu.

Funding

The Role of Inflammasome in the Pathogenesis of Atrial FibrillationR01HL136389 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI Na Li · 2017 to 2026
$5.6M
Cardiac fibroblast inflammasome and atrial myopathyR01HL163277 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI LI, NA · 2022 to 2025
$2.8M
Mechanisms of Lamin A/C-mediated Cardiac Conduction DisordersR01HL166832 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI Mihail Gabriel Chelu · 2024 to 2026
$1.9M
FKBP5 AND CARDIAC ARRHYTHMOGENESISR01HL164838 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI Na Li · 2024 to 2026
$1.7M
NHLBI NIH HHS R01 HL136389NHLBI NIH HHS R01 HL163277NHLBI NIH HHS R01 HL164838NHLBI NIH HHS R01 HL166832
6 · The paper itself

Abstract

backgroundAtrioventricular block (AVB) is a conduction system disorder that, when severe, results in pacemaker implantation. LMNA mutations affecting the nuclear envelope proteins lamin A/C have been linked to AVB in patients, yet the underlying mechanisms remain largely unclear. The authors identified a nonsense LMNA-R225X mutation in a kindred that was associated with progressive AVB and atrial arrhythmias, followed by left ventricular dysfunction.

objectivesThe aims of this study were to elucidate the mechanisms underlying LMNA-R225X-mediated AVB and to identify novel therapeutic targets for its treatment.

methodsLMNA-R225X-knock-in mice were generated using clustered regularly interspaced short palindromic repeats/Cas9 technology. Cardiac phenotype was characterized using surface electrocardiography, telemetry electrocardiography, programmed electrical stimulation, and echocardiography. Histology, immunofluorescence staining, Ca

resultsHomozygous LMNA-R225X mice displayed bradycardia and first-degree AVB before death at 2 weeks. Similar to patients, R225X-heterozygous mice exhibited age-dependent progressive AVB, ranging from first to second degree, and increased susceptibility to atrial fibrillation, preceding the development of cardiomyopathy. Specific knockdown of LMNA in cardiac conduction system pacemaker cells was sufficient to induce AVB. RNA sequencing analysis of atrioventricular node tissue revealed up-regulation of genes related to fibrosis and cellular hypertrophy, accompanied by down-regulation of the small-conductance calcium-activated potassium channel type 3 (SK3) channel. Ca

conclusionsThese findings establish a direct role of LMNA deficiency in AVB and reveal the SK3 channel as a therapeutic target for the management of AVB.

Indexed as

atrioventricular blocklamin A/Csmall-conductance calcium-activated potassium channel type 3 channel

Identifiers

PMID42569976
PMCPMC13692755

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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.