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Molecular and Translational Mechanisms of Cardiac Arrhythmias: From Oxidative Stress to Novel Therapeutic Strategies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 1878

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Guest Editor
Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
Interests: arrhythmias; atrial fibrillation; cardiac implantable devices

Special Issue Information

Dear Colleagues,

Cardiac arrhythmias, particularly atrial fibrillation, represent a major and growing global health burden, driven by complex interactions between molecular, cellular, and electrophysiological mechanisms. Increasing evidence highlights the central role of oxidative stress, inflammation, and structural and electrical remodeling in arrhythmia initiation and progression. This Special Issue will provide a comprehensive overview of the molecular and translational mechanisms underlying cardiac arrhythmias, bridging experimental discoveries and clinical relevance. We welcome original research articles and state-of-the-art reviews addressing mechanistic pathways, experimental models, and emerging therapeutic strategies, including pharmacological, device-based, and electrophysiological approaches. By integrating basic, translational, and clinically orientated research, this Special Issue will advance our understanding and foster innovation in arrhythmia prevention and treatment.

We are pleased to invite you to contribute to this Special Issue of International Journal of Molecular Sciences, focusing on the molecular and translational mechanisms of cardiac arrhythmias. Despite major advances in electrophysiology, arrhythmias such as atrial fibrillation remain associated with significant morbidity, mortality, and healthcare burdens. Growing evidence indicates that oxidative stress, molecular signaling pathways, and structural and electrical remodeling play a pivotal role in arrhythmogenesis. Understanding these mechanisms is essential in the development of more effective, personalized therapeutic strategies. This Special Issue will provide a platform for high-quality contributions that share molecular insights of translational and clinical relevance.

This Special Issue will highlight recent advances in the molecular, cellular, and translational mechanisms underlying cardiac arrhythmias and their therapeutic implications. This topic aligns closely with the scope of International Journal of Molecular Sciences by emphasizing molecular pathways, oxidative stress, signaling mechanisms, and experimental models while also extending to translational and clinically relevant applications. Fostering collaboration between basic scientists and clinicians, this Special Issue will comprise a focused yet comprehensive resource, including at least ten high-quality articles, with the potential for publication in book form.

Dr. Stefan Simović
Guest Editor

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Keywords

  • cardiac arrhythmias
  • atrial fibrillation
  • oxidative stress
  • molecular mechanisms
  • translational research
  • antiarrhythmic therapy
  • cardiac remodeling

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Published Papers (2 papers)

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Research

23 pages, 12554 KB  
Article
Effects of Antiarrhythmics on Cardiac Phenotype and Redox Balance in Spontaneously Hypertensive Rats
by Stefan M. Simović, Ivan M. Srejović, Goran T. Davidović, Maja D. Murić, Slobodanka L. Mitrović, Marko P. Ravić, Marijana M. Andjić, Marina R. Nikolić, Katarina G. Mihajlović, Nevena D. Lazarević, Sergey B. Bolevich, Aleksandra S. Orlova, Marina A. Fokina, Sergey E. Mironov, Vladimir Lj. Jakovljević and Jovana N. Novaković
Int. J. Mol. Sci. 2026, 27(14), 6490; https://doi.org/10.3390/ijms27146490 - 21 Jul 2026
Viewed by 332
Abstract
Arterial hypertension is a well-known risk factor for cardiac arrhythmias, while certain antihypertensive agents may also create conditions for arrhythmia occurrence. The aim of this study was to evaluate the effects of selected class III antiarrhythmic drugs on cardiac function and structure, as [...] Read more.
Arterial hypertension is a well-known risk factor for cardiac arrhythmias, while certain antihypertensive agents may also create conditions for arrhythmia occurrence. The aim of this study was to evaluate the effects of selected class III antiarrhythmic drugs on cardiac function and structure, as well as on oxidative stress status, in spontaneously hypertensive rats (SHRs). Male SHRs were treated for 4 weeks with dronedarone, amiodarone, or dofetilide. Cardiac function was assessed in vivo by echocardiography and ex vivo using the Langendorff model. Oxidative stress markers, myocardial morphology, and HSP70 and SERCA2 expression were analyzed. All drugs partially improved cardiac function in vivo, with dronedarone exerting the strongest antihypertensive effect. Ex vivo, dofetilide enhanced contractility and dronedarone reduced cardiac performance, whereas amiodarone showed intermediate effects. Oxidative stress was differentially modulated, with dofetilide and amiodarone improving antioxidant defenses, while dronedarone showed heterogeneous effects. Histologically, dofetilide preserved myocardial architecture most effectively, while amiodarone and dronedarone partially attenuated hypertensive remodeling. Treatments decreased HSP70 expression, while increasing SERCA2 expression, particularly in the dofetilide group. Class III antiarrhythmic drugs differentially affect cardiac function, redox balance, calcium handling, and myocardial remodeling in hypertension, which may contribute to their distinct antiarrhythmic and cardioprotective properties. Full article
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19 pages, 758 KB  
Article
Systemic Molecular Alterations of TP53, SIRT-1, and miR-34a Expression in Atrial Fibrillation: A Prospective Exploratory Biomarker Study
by Monika Różycka-Kosmalska, Izabela Szymczak-Pajor, Agnieszka Śliwińska, Małgorzata Kozłowska, Jerzy Krzysztof Wranicz and Marcin Kosmalski
Int. J. Mol. Sci. 2026, 27(12), 5633; https://doi.org/10.3390/ijms27125633 - 22 Jun 2026
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Abstract
p53, miR-34a, and SIRT-1 are involved in cellular stress responses, senescence, and inflammation—processes central to the pathophysiology of atrial fibrillation (AF). In this study, circulating TP53 and SIRT-1 serum miR-34a expression were determined in patients with and without AF, in order to assess [...] Read more.
p53, miR-34a, and SIRT-1 are involved in cellular stress responses, senescence, and inflammation—processes central to the pathophysiology of atrial fibrillation (AF). In this study, circulating TP53 and SIRT-1 serum miR-34a expression were determined in patients with and without AF, in order to assess their associations with AF. We also checked their potential diagnostic utility as systemic biomarkers associated with AF. The study included 189 adults, 94 AF+, 95 AF−. Clinical, anthropometric, and biochemical data were collected. Whole-blood TP53 and SIRT-1 mRNA expression and serum miR-34a expression were quantified by RT-qPCR. ROC analysis and Youden-derived odds ratios assessed exploratory diagnostic performance. AF patients had significantly higher expression of TP53 (0.0352 vs. 0.0253; p < 0.001) and miR-34a (0.0215 vs. 0.0099; p < 0.001), but significantly lower expression of SIRT-1 (0.0079 vs. 0.0145; p < 0.001). The level of SIRT-1 expression showed the highest discriminatory performance (exploratory AUC = 0.6987; p < 0.0001). TP53 expression levels exceeding 0.0295 were associated with nearly threefold higher odds of AF (OR = 2.92, 95% CI: 1.61–5.28, p = 0.0006), whereas the expression levels of SIRT-1 and miR-34a were not significantly associated with AF in cut-off analysis. In the AF group, a positive correlation was found between the expression of TP53 and SIRT-1 (Rho = 0.3609, p < 0.001); however, it was not consistent with a canonical model of miR-34a-mediated SIRT-1 suppression. In turn, the expression of miR-34a correlated positively with age and C-reactive protein level and negatively with estimated glomerular filtration rate (eGFR). The obtained results suggest that AF is associated with altered expression of circulating TP53, SIRT-1, and miR-34a. However, due to the fact that the expression levels were measured in peripheral compartments, and not in atrial tissue, the obtained results should not be interpreted as direct evidence of AF-related atrial remodeling. For these reasons, further investigations involving simultaneous measurements of the TP53/miR-34a/SIRT-1 regulatory axis, both in the circulating compartment and atrial tissue, should be performed. Full article
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