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Epigenetic Regulation and Molecular Mechanisms in Cardiovascular Diseases
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Epigenetic Regulation and Molecular Mechanisms in Cardiovascular Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 20 July 2026 | Viewed by 5441

Special Issue Editor

Dr. Paschalis Karakasis

E-Mail Website
Guest Editor
Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
Interests: cardiology; statistics; diabetes; heart failure; atrial fibrillation; atherosclerosis; SGLT-2 inhibitors; GLP-1 receptor agonists; myocardial infarction; ablation; arrhythmias
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Special Issue Information

Dear Colleagues,

Cardiovascular diseases remain a leading cause of death globally, yet the molecular pathways underlying their development are not fully understood. Recent advances highlight the critical role of epigenetic regulation—including DNA methylation, histone modifications, and non-coding RNAs—in modulating gene expression and driving cardiovascular pathology. This Special Issue of the International Journal of Molecular Sciences will focus on the latest molecular research exploring how epigenetic mechanisms influence key processes such as vascular inflammation, myocardial remodeling, atherosclerosis, and heart failure. We invite original research articles and reviews that present molecular data and mechanistic insights into the role of epigenetic regulation in cardiovascular diseases. Submissions employing state-of-the-art molecular techniques and addressing potential therapeutic implications are highly encouraged. We hope that this collection will provide a comprehensive view of the epigenetic landscape in cardiovascular diseases and foster the development of novel diagnostic and therapeutic strategies.

Dr. Paschalis Karakasis
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • epigenetic regulation
  • cardiovascular disease
  • DNA methylation
  • histone modifications
  • non-coding RNAs
  • vascular inflammation
  • myocardial remodeling
  • molecular mechanisms
  • thera-peutic targets

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Published Papers (3 papers)

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Review

32 pages, 1133 KB  
Review
Epigenetic Regulation and Molecular Mechanisms in Cardiovascular Diseases: A Review of Recent Advances and Therapeutic Implications
by Ewelina Młynarska, Kinga Bojdo, Anna Bulicz, Katarzyna Hossa, Wiktoria Lisińska, Paulina Stasiak, Jacek Rysz and Beata Franczyk
Int. J. Mol. Sci. 2026, 27(2), 983; https://doi.org/10.3390/ijms27020983 - 19 Jan 2026
Viewed by 1156
Abstract
Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, with growing evidence indicating that epigenetic mechanisms play a central role in their onset and progression. This review provides a comprehensive overview of current knowledge on the epigenetic regulation and molecular mechanisms involved [...] Read more.
Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, with growing evidence indicating that epigenetic mechanisms play a central role in their onset and progression. This review provides a comprehensive overview of current knowledge on the epigenetic regulation and molecular mechanisms involved in CVDs, as well as their potential therapeutic implications. The findings demonstrate that DNA methylation, histone modifications, and non-coding RNAs are key regulators of gene expression associated with cardiac hypertrophy, atherosclerosis, myocardial infarction, and heart failure. Interactions between epigenetic alterations and inflammatory or oxidative stress pathways further contribute to endothelial dysfunction and vascular remodeling. Emerging therapeutic strategies targeting these mechanisms, including histone deacetylase inhibitors, DNA methyltransferase inhibitors, and RNA-based therapeutics, show promising cardioprotective effects in experimental and early clinical studies. Overall, this review underscores the significance of epigenetic regulation in cardiovascular pathophysiology and highlights the potential of epigenetic-based interventions as a foundation for precision medicine and novel therapeutic approaches in cardiology. Full article
(This article belongs to the Special Issue Epigenetic Regulation and Molecular Mechanisms in Cardiovascular Diseases)
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29 pages, 1454 KB  
Review
From Vascular Dysfunction to Atherothrombosis: The Pivotal Role of Eicosanoids and Their Receptors in Platelet and Endothelial Imbalance: A Scoping Review
by Giovanna Ritorto, Sara Ussia, Roberta Macrì, Maria Serra, Annamaria Tavernese, Carmen Altomare, Denise Maria Dardano, Chiara Idone, Ernesto Palma, Carolina Muscoli, Maurizio Volterrani, Francesco Barillà, Vincenzo Mollace and Rocco Mollace
Int. J. Mol. Sci. 2026, 27(1), 162; https://doi.org/10.3390/ijms27010162 - 23 Dec 2025
Viewed by 673
Abstract
Vascular endothelium balances antithrombotic and anti-inflammatory activity to control blood vessel tone under physiological conditions. However, endothelial dysfunction impairs these processes, causing a state that promotes clotting and inflammation. Eicosanoids are a major class of bioactive lipid mediators crucial for modulating endothelial and [...] Read more.
Vascular endothelium balances antithrombotic and anti-inflammatory activity to control blood vessel tone under physiological conditions. However, endothelial dysfunction impairs these processes, causing a state that promotes clotting and inflammation. Eicosanoids are a major class of bioactive lipid mediators crucial for modulating endothelial and platelet function. Research has highlighted the roles of eicosanoids in vascular diseases, showing pro-inflammatory, prothrombotic, and protective activities. Specifically, prostaglandin E2 (PGE2) is crucial because of its major role in atherosclerosis development and progression, acting via EP receptors involved in forming, maintaining, and stabilizing atherosclerotic lesions, thereby making PGE2-EP signalling a specific target for treating cardiovascular diseases. This review will explore the evidence on eicosanoids and the role of their receptor modulation in platelet and vascular dysfunction in atherothrombosis. The studies included in this scoping review were retrieved from PubMed, Web of Science, Cochrane, and Scopus in accordance with the Preferred Reporting Items for Scoping Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) statement and the Population Intervention Comparison Outcome Population (PICO) framework. Eight clinical studies were found, which highlighted the crucial role of eicosanoids, like prostaglandins and their receptors, in endothelial and platelet dysfunction, and also how pharmacological mechanisms affect atherothrombosis. A new therapeutic approach for cardiovascular dysfunction is indicated by the recent findings, specifically against atherothrombosis, focusing on eicosanoids, their receptors, and processes like oxidative stress. Despite this evidence, there is a lack of comprehensive research results from scientific databases; therefore, further in vitro, in vivo, and clinical studies should be promoted to validate the preliminary results. Full article
(This article belongs to the Special Issue Epigenetic Regulation and Molecular Mechanisms in Cardiovascular Diseases)
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Graphical abstract

39 pages, 778 KB  
Review
Epigenetic Drivers of Atrial Fibrillation: Mechanisms, Biomarkers, and Therapeutic Targets
by Paschalis Karakasis, Panagiotis Theofilis, Nikias Milaras, Panayotis K. Vlachakis, Dimitrios Patoulias, Theodoros Karamitsos, Antonios P. Antoniadis and Nikolaos Fragakis
Int. J. Mol. Sci. 2025, 26(11), 5253; https://doi.org/10.3390/ijms26115253 - 29 May 2025
Cited by 14 | Viewed by 3098
Abstract
Atrial fibrillation (AF) is the most prevalent sustained arrhythmia, associated with significant morbidity, mortality, and healthcare burdens. Despite therapeutic advances, recurrence rates remain high, particularly in persistent AF, underscoring the need for deeper mechanistic insight. Epigenetic regulation—comprising DNA methylation, histone modifications, chromatin remodeling, [...] Read more.
Atrial fibrillation (AF) is the most prevalent sustained arrhythmia, associated with significant morbidity, mortality, and healthcare burdens. Despite therapeutic advances, recurrence rates remain high, particularly in persistent AF, underscoring the need for deeper mechanistic insight. Epigenetic regulation—comprising DNA methylation, histone modifications, chromatin remodeling, RNA methylation, and non-coding RNAs—has emerged as a key contributor to the structural, electrical, and inflammatory remodeling underlying AF. These mechanisms operate at the interface of genetic susceptibility and environmental exposure, offering a dynamic framework for understanding disease progression. Systemic stressors such as aging, obesity, diabetes, hypertension, hypoxia, and alcohol have been shown to induce epigenetic reprogramming in atrial tissue, further promoting atrial cardiomyopathy and arrhythmogenesis. Additionally, circulating epigenetic markers, particularly microRNAs, are being investigated for their potential in AF diagnosis, risk stratification, and therapeutic monitoring. Therapeutic strategies targeting epigenetic pathways—ranging from histone deacetylase inhibitors and miRNA-based therapeutics to CRISPR/dCas9-mediated epigenome editing—are under investigation. Additionally, sodium-glucose cotransporter 2 inhibitors may indirectly influence epigenetic programs and miRNA expression relevant to atrial remodeling. While promising, these approaches require further validation in terms of safety, delivery specificity, and long-term efficacy. High-resolution epigenomic mapping and integrative multi-omic approaches may enhance understanding of AF heterogeneity and enable personalized treatment strategies. This review provides an integrated appraisal of epigenetic mechanisms in AF and outlines their emerging diagnostic and therapeutic relevance. Full article
(This article belongs to the Special Issue Epigenetic Regulation and Molecular Mechanisms in Cardiovascular Diseases)
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