ArticleInternational journal of molecular sciences2024
Interleukin-6 Modulates the Expression and Function of HCN Channels: A Link Between Inflammation and Atrial Electrogenesis.
Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Preprocedural Biomarkers of Inflammation and Fibrosis and Echocardiographic Markers of Myocardial Remodeling in New-Onset Conduction Disorders After Transcatheter Aortic Valve Implantation.Medicina (Kaunas, Lithuania) · 2026Observational
- Systemic Inflammation Is Associated with Resting Premature Atrial and Ventricular Contractions in American Older Adults.The Journal of innovations in cardiac rhythm management · 2026Article
- The Evolving Role of Ivabradine for Focal Atrial Tachycardia: A Systematic Review.Journal of arrhythmia · 2026Article
- The Interplay Between Periodontitis and Atrial Fibrillation: Inflammation as a Common Pathophysiological Bridge.International journal of molecular sciences · 2026Review
- Immunomodulatory Potential of Kaempferol Isolated fromInternational journal of molecular sciences · 2025Article
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Authors and funding
11 authors.
Funding
Abstract
Inflammatory cytokines, including interleukin 6 (IL6), are associated with ion channel remodeling and enhance the propensity to alterations in cardiac rhythm generation and propagation, in which the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a crucial role. Hence, we investigated the consequences of exposure to IL6 on HCN channels in cell models and human atrial biopsies. In murine atrial HL1 cells and in cardiomyocytes derived from human induced pluripotent stem cells (hiPS-CMs), IL6 elicited STAT3 phosphorylation, a receptor-mediated downstream signaling. Downregulation of HCN1,2,4 by IL6 was observed after 24-48 h; in hiPS-CMs, this effect was reverted by 24 h of application of tocilizumab, a human IL6 receptor antagonist. In parallel, hiPS-CM action potentials (APs) showed a reduced spontaneous frequency. Moreover, we assessed IL6 and HCN expression in dilated left atrial samples from patients with mitral valve disease, an AF-prone condition. IL6 levels were increased in dilated atria compared to controls and positively correlated with echocardiographic atrial dimensions. Interestingly, the highest IL6 transcript levels and the lowest HCN4 and HCN2 expression were in these samples. In conclusion, our data uncovered a novel link between IL6 and cardiac HCN channels, potentially contributing to atrial electrical disturbances and a higher risk of dysrhythmias in conditions with elevated IL6 levels.
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