GJA1-20k Rescues Cx43 Localization and Arrhythmias in Arrhythmogenic Cardiomyopathy
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Experimental approaches to enhance gap junction integrity, such as delivery of the truncated Cx43 isoform GJA1-20k, have improved electrical coupling and reduced arrhythmias in ACM models.
“Experimental approaches to enhance gap junction integrity, such as delivery of the truncated Cx43 isoform, GJA1-20k, and other strategies, have improved electrical coupling and reduced arrhythmias in ACM models [96,121].”
From A Paradigm Shift: Arrhythmogenic Cardiomyopathy Is an Inflammatory Disease (2026) · cites this paper as [96]
In the paper’s main text (page unavailable), AAV9-mediated GJA1-20k delivery restored Cx43 localization at intercalated discs and significantly reduced ventricular arrhythmias in Dsg2−/− ACM mice. The paper does not report a direct measure of improved electrical coupling; it reports gap-junction localization instead. (LLM, conf=0.86)
Experimental — accuracy not yet measuredGene therapy with AAV9-GJA1-20k rescued gap junction distribution and reduced VAs in an ACM mouse model.
“A recent study demonstrated that gene therapy delivered using an exogenous AAV9-GJA1-20k, a 20 kDa isoform of Cx43, successfully rescued gap junction distribution and reduced VAs in an ACM mouse model [96], further supporting the critical role, or lack thereof, of Cx43 in ACM.”
From A Paradigm Shift: Arrhythmogenic Cardiomyopathy Is an Inflammatory Disease (2026) · cites this paper as [96]
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Cites
Central role for GSK3β in the pathogenesis of arrhythmogenic cardiomyopathy
Chelko, S. P., Asimaki, A., Andersen, P., Bedja, D., Amat-Alarcon, N., DeMazumder, D., Jasti, R., MacRae, C. A., Leber, R., Kleber, A. G., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.85923 · Cited by 180 · see citing works
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Research works printed but not linked: 4
- [1]van Opbergen CJM, Bagwan N, Maurya SR, Kim JC, Smith AN, Blackwell DJ, Johnston JN, Knollmann BC, Cerrone M, Lundby A, Exercise Causes Arrhythmogenic Remodeling of Intracellular Calcium Dynamics in Plakophilin-2-Deficient Hearts. Circulation 2022; 145: 1480– 1496. 35491884 PMC9086182
- [2]Asimaki A, Kleber AG, MacRae CA, Saffitz JE. Arrhythmogenic Cardiomyopathy - New Insights into Disease Mechanisms and Drug Discovery. Prog Pediatr Cardiol 2014; 37: 3– 7. 25506190 PMC4260412
- [4]Xiao S, Shimura D, Baum R, Hernandez DM, Agvanian S, Nagaoka Y, Katsumata M, Lampe PD, Kleber AG, Hong T, Auxiliary trafficking subunit GJA1-20k protects connexin-43 from degradation and limits ventricular arrhythmias. J Clin Invest 2020; 130: 4858– 4870. 32525845 PMC7456223
- [5]Basheer WA, Fu Y, Shimura D, Xiao S, Agvanian S, Hernandez DM, Hitzeman TC, Hong T, Shaw RM. Stress response protein GJA1-20k promotes mitochondrial biogenesis, metabolic quiescence, and cardioprotection against ischemia/reperfusion injury. JCI Insight 2018; 3. PMC6237442 30333316
Cited by
Sorted by citations
A Paradigm Shift: Arrhythmogenic Cardiomyopathy Is an Inflammatory Disease
Ariyaratne, G. H. D. N., Villatore, A., Peretto, G., & Chelko, S. P. (2026) · Cells · doi:10.3390/cells15100868 · Cited by 2 · see citing works
- Authors
- Palatinus, J. A., Valdez, S., Taylor, L., Whisenant, C., Selzman, C. H., Drakos, S. G., Ranjan, R., Hong, T., Saffitz, J. E., & Shaw, R. M.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- University of Utah (US)
- Corresponding author
- Shaw, Robin M.
- ORCID
- Venue
- Circulation Research
- Published
- 2023-03-17
- Volume
- 132
- Issue
- 6
- Pages
- 744-746
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC10314823
- OpenAlex
- W4321496535
- Cited by
- 40
- References
- 1
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 9 · 2023: 5
- FWCI
- 7.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Nora Eccles Treadwell Foundation
- National Institutes of Health
- National Institute on Aging (R21AG074593)
- National Heart, Lung, and Blood Institute (R01HL152691, R01HL159983, K08HL155886, T32HL007576)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Keywords
- connexin 43, arrhythmogenic cardiomyopathy, cardiac arrhythmias, gap junctions
- MeSH terms
- Arrhythmias, Cardiac, Humans, Cardiomyopathies, Myocardium, Gap Junctions, Connexin 43
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