ArticleThe Journal of clinical investigation2020
Prevention of connexin-43 remodeling protects against Duchenne muscular dystrophy cardiomyopathy.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 76 citations in OpenAlex.
- Role of NADPH oxidase 2-derived reactive oxygen species in cardiac electrophysiological disorders.Channels (Austin, Tex.) · 2026Review
- Vasohibin 1 acts as a key regulator of arrhythmogenesis in pressure-overload-induced cardiac hypertrophy.Acta pharmacologica Sinica · 2026Article
- Phospho-mimic βIII-tubulin rescues microtubule and cardiac defects in Duchenne muscular dystrophy mice.Journal of molecular and cellular cardiology · 2026Article
- Cardiac Impulse Propagation: An Integrated View.JACC. Basic to translational science · 2026Review
- Connexin43 Deficiency Leads to Ventricular Arrhythmias by Reprogramming Proline Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- HIV heart inflammation is mediated by HIV infected myeloid cells, HIV-tat secretion, and aberrant function of Connexin43-containing channels.Scientific reports · 2026Article
- Potential Involvement of Ferroptosis in Duchenne Muscular Dystrophy-Associated Cardiomyopathy.Biomedicines · 2026Article
- Endothelial TRPV4-Cx43 signalling complex regulates vasomotor tone in resistance arteries.The Journal of physiology · 2025Article
- Fibroblast-Restricted Inflammasome Activation Promotes Atrial Fibrillation and Heart Failure With Diastolic Dysfunction.JACC. Basic to translational science · 2025Article
- Extensive striated muscle damage in a rat model of Duchenne muscular dystrophy with Dmd exons 10-17 duplication.Skeletal muscle · 2025Article
- Overexpression of Cx43: Is It an Effective Approach for the Treatment of Cardiovascular Diseases?Biomolecules · 2025Review
- Unveiling the native architecture of adult cardiac tissue using the 3D-NaissI method.Cellular and molecular life sciences : CMLS · 2025Article
- Conduction defects and arrhythmias inFrontiers in physiology · 2025Article
- Article
- Endothelial TRPV4/Cx43 Signaling Complex Regulates Vasomotor Tone in Resistance Arteries.bioRxiv : the preprint server for biology · 2024Article
- Differential Regulation of Hemichannels and Gap Junction Channels by RhoA GTPase and Actin Cytoskeleton: A Comparative Analysis of Cx43 and Cx26.International journal of molecular sciences · 2024Article
- Low-Dose Colchicine Ameliorates Doxorubicin Cardiotoxicity Via Promoting Autolysosome Degradation.Journal of the American Heart Association · 2024Article
- KLF5 promotes the ossification process of ligamentum flavum by transcriptionally activating CX43.Journal of orthopaedic surgery and research · 2024Article
- Colchicine Inhibits NETs and Alleviates Cardiac Remodeling after Acute Myocardial Infarction.Cardiovascular drugs and therapy · 2024Article
- Casein Kinase 1 Phosphomimetic Mutations Negatively Impact Connexin-43 Gap Junctions in Human Pluripotent Stem Cell-Derived Cardiomyocytes.Biomolecules · 2024Article
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Aberrant expression of the cardiac gap junction protein connexin-43 (Cx43) has been suggested as playing a role in the development of cardiac disease in the mdx mouse model of Duchenne muscular dystrophy (DMD); however, a mechanistic understanding of this association is lacking. Here, we identified a reduction of phosphorylation of Cx43 serines S325/S328/S330 in human and mouse DMD hearts. We hypothesized that hypophosphorylation of Cx43 serine-triplet triggers pathological Cx43 redistribution to the lateral sides of cardiomyocytes (remodeling). Therefore, we generated knockin mdx mice in which the Cx43 serine-triplet was replaced with either phospho-mimicking glutamic acids (mdxS3E) or nonphosphorylatable alanines (mdxS3A). The mdxS3E, but not mdxS3A, mice were resistant to Cx43 remodeling, with a corresponding reduction of Cx43 hemichannel activity. MdxS3E cardiomyocytes displayed improved intracellular Ca2+ signaling and a reduction of NADPH oxidase 2 (NOX2)/ROS production. Furthermore, mdxS3E mice were protected against inducible arrhythmias, related lethality, and the development of cardiomyopathy. Inhibition of microtubule polymerization by colchicine reduced both NOX2/ROS and oxidized CaMKII, increased S325/S328/S330 phosphorylation, and prevented Cx43 remodeling in mdx hearts. Together, these results demonstrate a mechanism of dystrophic Cx43 remodeling and suggest that targeting Cx43 may be a therapeutic strategy for preventing heart dysfunction and arrhythmias in DMD patients.
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