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Biomedicines
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Epigenetics and Novel Opportunities for Precision Medicine and Personalized Therapy...
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Epigenetics and Novel Opportunities for Precision Medicine and Personalized Therapy of Major Cardiovascular Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular Genetics and Genetic Diseases".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 8768

Special Issue Editors

Dr. Giuditta Benincasa

E-Mail Website
Guest Editor
Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
Interests: clinical research; epigenetics; network analysis; novel potential biomarkers; drug targets; precision medicine; personalized therapy of cardiopulmonary
Prof. Dr. Paola Bontempo

E-Mail Website
Guest Editor
Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, Italy
Interests: anthocyanin; metabolite; natural compounds; antioxidant; cancer; cell proliferation; cell differentiation; bioactive molecules; epigenetics; epidrugs; molecular simulations; endocrine disruptors
Special Issues, Collections and Topics in MDPI journals
Dr. Malik Bisserier

E-Mail Website
Guest Editor
Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Interests: epigenetics; gene regulation; DNA methylation; histone modification; pulmonary hypertension; gene therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the era of cardiovascular precision medicine and personalized therapy, physicians are motivated to identify customized approaches. The latest progress indicates that direct epigenetic-sensitive modifications (DNA methylation and histone modifications) may be useful to shift away from diagnosis in advanced, symptomatic states towards an earlier prediction of cardiac events. Profiling patient-derived epigenetic changes at the genome-wide level in conjunction with clinical data will lead to the identification of predictive, diagnostic, and prognostic biomarkers as well as additional therapeutic strategies for major cardiovascular diseases. “Omics” platforms, network analysis, and artificial intelligence represent the most useful integrated approaches to reach cardiovascular precision medicine and personalized therapy. The first goal of this Special Issue is to collect big data generated from epigenome-wide association studies (EWAS) in order to identify novel molecular routes involved in the pathogenesis of major cardiovascular diseases that have the highest potential of being translated into biomarkers for clinical practice. Our second aim is to compile data on natural compounds, which may act as “epidrugs” able to prevent or reverse cardiac damage via remodeling the epigenome, mainly in cardiac and endothelial cells.

Dr. Giuditta Benincasa
Prof. Dr. Paola Bontempo
Dr. Malik Bisserier
Guest Editors

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 100 words) can be sent to the Editorial Office for announcement on this website.

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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • cardiovascular diseases
  • clinical epigenetics
  • biomarkers
  • drug targets
  • epigenome-wide association studies
  • DNA methylation
  • histone modification
  • natural compounds
  • epidrugs
  • bioinformatics
  • network analysis
  • artificial intelligence

Published Papers (6 papers)

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Research

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14 pages, 1311 KiB  
Article
Plasma hsa-miR-22-3p Might Serve as an Early Predictor of Ventricular Function Recovery after ST-Elevation Acute Myocardial Infarction
by Liana Maries, Alexandra Ioana Moatar, Aimee Rodica Chis, Catalin Marian, Constantin Tudor Luca, Ioan-Ovidiu Sirbu and Dan Gaiță
Biomedicines 2023, 11(8), 2289; https://doi.org/10.3390/biomedicines11082289 - 17 Aug 2023
Cited by 2 | Viewed by 749
Abstract
Left ventricle remodeling (LVR) after acute myocardial infarction (aMI) leads to impairment of both systolic and diastolic function, a major contributor to heart failure (HF). Despite extensive research, predicting post-aMI LVR and HF is still a challenge. Several circulant microRNAs have been proposed [...] Read more.
Left ventricle remodeling (LVR) after acute myocardial infarction (aMI) leads to impairment of both systolic and diastolic function, a major contributor to heart failure (HF). Despite extensive research, predicting post-aMI LVR and HF is still a challenge. Several circulant microRNAs have been proposed as LVR predictors; however, their clinical value is controversial. Here, we used real-time quantitative polymerase chain reaction (qRT-PCR) to quantify hsa-miR-22-3p (miR-22) plasma levels on the first day of hospital admission of ST-elevation aMI (STEMI) patients. We analyzed miR-22 correlation to the patients’ clinical and paraclinical variables and evaluated its ability to discriminate between post-aMI LVR and non-LVR. We show that miR-22 is an excellent aMI discriminator and can distinguish between LVR and non-LVR patients. The discriminative performance of miR-22 significantly improves the predictive power of a multiple logistic regression model based on four continuous variables (baseline ejection fraction and end-diastolic volume, CK-MB, and troponin). Furthermore, we found that diabetes mellitus, hematocrit level, and the number of erythrocytes significantly influence its levels. These data suggest that miR-22 might be used as a predictor of ventricular function recovery in STEMI patients. Full article
(This article belongs to the Special Issue Epigenetics and Novel Opportunities for Precision Medicine and Personalized Therapy of Major Cardiovascular Diseases)
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18 pages, 2963 KiB  
Article
Cholesterol-Related lncRNAs as Response Predictors of Atorvastatin Treatment in Chilean Hypercholesterolemic Patients: A Pilot Study
by Isis Paez, Yalena Prado, Pía Loren, Carmen G. Ubilla, Nelia Rodríguez and Luis A. Salazar
Biomedicines 2023, 11(3), 742; https://doi.org/10.3390/biomedicines11030742 - 01 Mar 2023
Viewed by 1241
Abstract
Statins are currently the treatment of choice for hypercholesterolemia. However, wide interindividual variability has been observed in the response to treatment. Recent studies have reported the role of lncRNAs in the metabolism of lipids; nevertheless, there are few studies to date that show [...] Read more.
Statins are currently the treatment of choice for hypercholesterolemia. However, wide interindividual variability has been observed in the response to treatment. Recent studies have reported the role of lncRNAs in the metabolism of lipids; nevertheless, there are few studies to date that show their role in the response to treatment with statins. Thus, the aim of this study was to assess the levels of expression of three lncRNAs (RP1-13D10.2; MANTIS; lncHR1) associated with genes involved in cholesterol homeostasis in leukocyte cells of hypercholesterolemic patients after treatment with atorvastatin and compare them with levels in subjects with normal cholesterol levels. A secondary aim was to assess the levels of expression in monocytic THP-1 cells differentiated to macrophages. The study included 20 subjects with normal cholesterol (NC) levels and 20 individuals with hypercholesterolemia (HC). The HC patients were treated with atorvastatin (20 mg/day/4 weeks). THP-1 cells were differentiated to macrophages with PMA and treated with different doses of atorvastatin for 24 h. Expression of lncRNAs was determined by RT-qPCR. The lncRNAs RP1-13D10.2 (p < 0.0001), MANTIS (p = 0.0013) and lncHR1 (p < 0.0001) presented increased expression in HC subjects compared with NC subjects. Furthermore, atorvastatin had a negative regulatory effect on the expression of lncHR1 (p < 0.0001) in HC subjects after treatment. In vitro, all the lncRNAs showed significant differences in expression after atorvastatin treatment. Our findings show that the lncRNAs tested present differential expression in HC patients and play a role in the variability reported in the response to atorvastatin treatment. Further research is needed to clarify the biological impact of these lncRNAs on cholesterol homeostasis and treatment with statins. Full article
(This article belongs to the Special Issue Epigenetics and Novel Opportunities for Precision Medicine and Personalized Therapy of Major Cardiovascular Diseases)
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Review

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16 pages, 2989 KiB  
Review
Switch-Independent 3A: An Epigenetic Regulator in Cancer with New Implications for Pulmonary Arterial Hypertension
by Katherine Jankowski, Vineeta Jagana, Malik Bisserier and Lahouaria Hadri
Biomedicines 2024, 12(1), 10; https://doi.org/10.3390/biomedicines12010010 - 20 Dec 2023
Cited by 2 | Viewed by 1069
Abstract
Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA, play a crucial role in the regulation of gene expression and are pivotal in biological processes like apoptosis, cell proliferation, and differentiation. SIN3a serves as a scaffold protein and facilitates interactions with transcriptional [...] Read more.
Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA, play a crucial role in the regulation of gene expression and are pivotal in biological processes like apoptosis, cell proliferation, and differentiation. SIN3a serves as a scaffold protein and facilitates interactions with transcriptional epigenetic partners and specific DNA-binding transcription factors to modulate gene expression by adding or removing epigenetic marks. However, the activation or repression of gene expression depends on the factors that interact with SIN3a, as it can recruit both transcriptional activators and repressors. The role of SIN3a has been extensively investigated in the context of cancer, including melanoma, lung, and breast cancer. Our group is interested in defining the roles of SIN3a and its partners in pulmonary vascular disease. Pulmonary arterial hypertension (PAH) is a multifactorial disease often described as a cancer-like disease and characterized by disrupted cellular metabolism, sustained vascular cell proliferation, and resistance to apoptosis. Molecularly, PAH shares many common signaling pathways with cancer cells, offering the opportunity to further consider therapeutic strategies used for cancer. As a result, many signaling pathways observed in cancer were studied in PAH and have encouraged new research studying SIN3a’s role in PAH due to its impact on cancer growth. This comparison offers new therapeutic options. In this review, we delineate the SIN3a-associated epigenetic mechanisms in cancer and PAH cells and highlight their impact on cell survival and proliferation. Furthermore, we explore in detail the role of SIN3a in cancer to provide new insights into its emerging role in PAH pathogenesis. Full article
(This article belongs to the Special Issue Epigenetics and Novel Opportunities for Precision Medicine and Personalized Therapy of Major Cardiovascular Diseases)
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17 pages, 485 KiB  
Review
Panoramic on Epigenetics in Coronary Artery Disease and the Approach of Personalized Medicine
by Marcello Bergonzini, Francesco Loreni, Antonio Lio, Marco Russo, Guglielmo Saitto, Antonio Cammardella, Francesco Irace, Corrado Tramontin, Massimo Chello, Mario Lusini, Antonio Nenna, Chiara Ferrisi, Federico Ranocchi and Francesco Musumeci
Biomedicines 2023, 11(10), 2864; https://doi.org/10.3390/biomedicines11102864 - 23 Oct 2023
Cited by 1 | Viewed by 1275
Abstract
Epigenetic modifications play a fundamental role in the progression of coronary artery disease (CAD). This panoramic review aims to provide an overview of the current understanding of the epigenetic mechanisms involved in CAD pathogenesis and highlights the potential implications for personalized medicine approaches. [...] Read more.
Epigenetic modifications play a fundamental role in the progression of coronary artery disease (CAD). This panoramic review aims to provide an overview of the current understanding of the epigenetic mechanisms involved in CAD pathogenesis and highlights the potential implications for personalized medicine approaches. Epigenetics is the study of heritable changes that do not influence alterations in the DNA sequence of the genome. It has been shown that epigenetic processes, including DNA/histone methylation, acetylation, and phosphorylation, play an important role. Additionally, miRNAs, lncRNAs, and circRNAs are also involved in epigenetics, regulating gene expression patterns in response to various environmental factors and lifestyle choices. In the context of CAD, epigenetic alterations contribute to the dysregulation of genes involved in inflammation, oxidative stress, lipid metabolism, and vascular function. These epigenetic changes can occur during early developmental stages and persist throughout life, predisposing individuals to an increased risk of CAD. Furthermore, in recent years, the concept of personalized medicine has gained significant attention. Personalized medicine aims to tailor medical interventions based on an individual’s unique genetic, epigenetic, environmental, and lifestyle factors. In the context of CAD, understanding the interplay between genetic variants and epigenetic modifications holds promise for the development of more precise diagnostic tools, risk stratification models, and targeted therapies. This review summarizes the current knowledge of epigenetic mechanisms in CAD and discusses the fundamental principles of personalized medicine. Full article
(This article belongs to the Special Issue Epigenetics and Novel Opportunities for Precision Medicine and Personalized Therapy of Major Cardiovascular Diseases)
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14 pages, 1780 KiB  
Review
Epigenetics in Heart Failure: Role of DNA Methylation in Potential Pathways Leading to Heart Failure with Preserved Ejection Fraction
by Simon W. Rabkin and Chenille N. Wong
Biomedicines 2023, 11(10), 2815; https://doi.org/10.3390/biomedicines11102815 - 17 Oct 2023
Cited by 1 | Viewed by 1202
Abstract
This review will focus on epigenetic modifications utilizing the DNA methylation mechanism, which is potentially involved in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). The putative pathways of HFpEF will be discussed, specifically myocardial fibrosis, myocardial inflammation, sarcoplasmic reticulum Ca [...] Read more.
This review will focus on epigenetic modifications utilizing the DNA methylation mechanism, which is potentially involved in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). The putative pathways of HFpEF will be discussed, specifically myocardial fibrosis, myocardial inflammation, sarcoplasmic reticulum Ca2+-ATPase, oxidative–nitrosative stress, mitochondrial and metabolic defects, as well as obesity. The relationship of HFpEF to aging and atrial fibrillation will be examined from the perspective of DNA methylation. Full article
(This article belongs to the Special Issue Epigenetics and Novel Opportunities for Precision Medicine and Personalized Therapy of Major Cardiovascular Diseases)
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13 pages, 562 KiB  
Review
The Current Therapeutic Role of Chromatin Remodeling for the Prognosis and Treatment of Heart Failure
by Lindsay Kraus and Brianna Beavens
Biomedicines 2023, 11(2), 579; https://doi.org/10.3390/biomedicines11020579 - 16 Feb 2023
Viewed by 2097
Abstract
Cardiovascular diseases are a major cause of death globally, with no cure to date. Many interventions have been studied and suggested, of which epigenetics and chromatin remodeling have been the most promising. Over the last decade, major advancements have been made in the [...] Read more.
Cardiovascular diseases are a major cause of death globally, with no cure to date. Many interventions have been studied and suggested, of which epigenetics and chromatin remodeling have been the most promising. Over the last decade, major advancements have been made in the field of chromatin remodeling, particularly for the treatment of heart failure, because of innovations in bioinformatics and gene therapy. Specifically, understanding changes to the chromatin architecture have been shown to alter cardiac disease progression via variations in genomic sequencing, targeting cardiac genes, using RNA molecules, and utilizing chromatin remodeler complexes. By understanding these chromatin remodeling mechanisms in an injured heart, treatments for heart failure have been suggested through individualized pharmaceutical interventions as well as biomarkers for major disease states. By understanding the current roles of chromatin remodeling in heart failure, a potential therapeutic approach may be discovered in the future. Full article
(This article belongs to the Special Issue Epigenetics and Novel Opportunities for Precision Medicine and Personalized Therapy of Major Cardiovascular Diseases)
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