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Antioxidants
Special Issues
Antioxidants in Cardiovascular Medicine: Emerging Trends and Future Perspectives
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Antioxidants in Cardiovascular Medicine: Emerging Trends and Future Perspectives

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (30 April 2026) | Viewed by 7664

Special Issue Editors

Dr. Matteo Becatti

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Guest Editor
Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Firenze, 50121 Firenze, Italy
Interests: thrombosis; fibrinogen; oxidative stress; protein structure
Special Issues, Collections and Topics in MDPI journals
Dr. Claudia Fiorillo

E-Mail Website
Guest Editor
Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence, Viale Morgagni 50, 50134 Florence, Italy
Interests: redox markers; antioxidant capacity; post-translational oxidative modification; ROS sources
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to introduce our upcoming Special Issue, which will explore the evolving role of antioxidants in cardiovascular medicine. Oxidative stress is increasingly recognized as a key contributor to the pathogenesis and progression of cardiovascular diseases (CVDs). As such, the potential of antioxidant-based therapies to mitigate oxidative damage and improve cardiovascular outcomes has garnered significant scientific and clinical interest.

This Special Issue aims to provide a comprehensive perspective on the latest advancements in antioxidant research, with a focus on novel compounds, molecular mechanisms, and clinical applications in CVD management. We welcome original research and review articles that address the following:

  • The role of oxidative stress and redox signaling in cardiovascular pathophysiology, including endothelial dysfunction, inflammation, myocardial remodeling, and vascular aging;
  • Innovative antioxidant therapies, including synthetic and natural compounds, targeted delivery systems, and combination approaches;
  • Preclinical and clinical evidence evaluating the efficacy of antioxidants in conditions such as atherosclerosis, hypertension, heart failure, and ischemic heart disease;
  • Dietary and lifestyle interventions that enhance antioxidant defenses and reduce cardiovascular risk;
  • Emerging biomarkers and novel methodologies for assessing oxidative stress and antioxidant efficacy in cardiovascular research;
  • The role of artificial intelligence (AI) and machine learning (ML) in predicting oxidative stress-related cardiovascular risks, personalizing antioxidant therapies, and analyzing large-scale omics data;
  • Computational modeling-and AI-driven drug discovery for the identification of new antioxidant compounds and their cardioprotective effects;
  • Big data analytics for evaluating population-based trends and the effectiveness of antioxidant-based interventions in real-world cardiovascular health.

By gathering contributions from experts across diverse fields, this Special Issue aims to bridge the gap between fundamental research and clinical applications, fostering a deeper understanding of antioxidant strategies in cardiovascular health. We encourage multidisciplinary perspectives, including insights from pharmacology, molecular biology, nutrition, artificial intelligence, and clinical medicine.

We look forward to your valuable contributions and to advancing the discussion on how antioxidant-based interventions, enhanced by AI-driven approaches, can shape the future of cardiovascular medicine.

Dr. Matteo Becatti
Dr. Claudia Fiorillo
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 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. Antioxidants 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 2900 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 disease
  • CVD
  • atherosclerosis
  • hypertension
  • heart failure
  • ischemic heart disease
  • vascular aging
  • myocardial remodeling

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  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
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Further information on MDPI's Special Issue policies can be found here.

Published Papers (6 papers)

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Research

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28 pages, 14056 KB  
Article
Anti-Atherogenic Actions of Pomegranate Polyphenol Punicalagin and Its Metabolites: In Vitro Effects on Vascular Cells and In Vivo Atheroprotection by Urolithin A via Anti-Inflammatory and Plaque-Stabilising Mechanisms
by Sulaiman Alalawi, Daniah Rifqi, Alaa Alhamadi, Reem Alotibi, Fahad Alradi, Nouf Alshehri, Yee-Hung Chan, Jing Chen, Faizah Albalawi, Sarab Taha, Nabras Al-Mahrami, Irina A. Guschina, Timothy R. Hughes and Dipak P. Ramji
Antioxidants 2026, 15(4), 507; https://doi.org/10.3390/antiox15040507 - 20 Apr 2026
Viewed by 1905
Abstract
Nutraceuticals are emerging as promising agents for the prevention and treatment of atherosclerosis, particularly in light of the limitations associated with current pharmacotherapies. Pomegranate-derived polyphenols, especially punicalagin (PC), possess multiple cardioprotective properties. However, their direct biological effects are constrained by poor absorption and [...] Read more.
Nutraceuticals are emerging as promising agents for the prevention and treatment of atherosclerosis, particularly in light of the limitations associated with current pharmacotherapies. Pomegranate-derived polyphenols, especially punicalagin (PC), possess multiple cardioprotective properties. However, their direct biological effects are constrained by poor absorption and low bioavailability. Instead, many of their actions are mediated by gut microbiota-derived metabolites known as urolithins. Despite this, the roles of PC and its metabolites in atherosclerosis remain inadequately defined. The objective of this study was to investigate the anti-atherogenic effects and underlying mechanisms of PC and its major metabolites—ellagic acid and urolithins A, B, C, and D—using in vitro and in vivo approaches. In vitro, these compounds broadly inhibited key pro-atherogenic processes in macrophages and endothelial cells, including reactive oxygen species production and inflammatory gene expression, with notable metabolite-specific differences. Urolithin A (UA), identified as the most effective compound, was further evaluated in LDL receptor-deficient mice fed a high-fat diet. UA supplementation improved peripheral blood immune cell profile, reduced atherosclerotic plaque burden and inflammation, and enhanced markers of plaque stability. RNA sequencing of the thoracic aorta revealed key molecular pathways underlying the protective actions of UA. Collectively, these findings highlight the therapeutic potential of PC-derived metabolites, particularly UA, in combating atherosclerosis and support the need for future human clinical studies. Full article
(This article belongs to the Special Issue Antioxidants in Cardiovascular Medicine: Emerging Trends and Future Perspectives)
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19 pages, 452 KB  
Article
Circulating Biomarkers in Elderly Patients with Heart Failure: A Real-Life Study
by Velia Cassano, Caterina Gabriele, Maria Rosangela Scarcelli, Giuseppe Armentaro, Giandomenico Severini, Domenico Martire, Carlo Alberto Pastura, Sofia Miceli, Marta Letizia Hribal, Giuseppe Massimo Claudio Rosano, Marco Gaspari and Angela Sciacqua
Antioxidants 2026, 15(3), 305; https://doi.org/10.3390/antiox15030305 - 28 Feb 2026
Viewed by 508
Abstract
Background: Heart failure (HF) is a clinical syndrome that involves multiple interconnected pathways. Circulating biomarkers in HF emerged as powerful tools for risk stratification, diagnostic confirmation, prognostic assessment, and monitoring of treatment efficacy. The aim of the present study was to evaluate [...] Read more.
Background: Heart failure (HF) is a clinical syndrome that involves multiple interconnected pathways. Circulating biomarkers in HF emerged as powerful tools for risk stratification, diagnostic confirmation, prognostic assessment, and monitoring of treatment efficacy. The aim of the present study was to evaluate circulating levels of biomarkers in elderly patients with improved HF ejection fraction, previously with left ventricular ejection fraction (LVEF) <40%, after six months of drug therapy optimisation. Methods: We enrolled 100 HFimpEF outpatients. All patients provided medical history and underwent physical examination at baseline and after six months of follow-up. The serum values of circulating biomarkers were assessed with an ELISA test. Proteomic analysis was performed on serum samples collected from a subset of 13 patients at baseline and after six months of follow-up. Results: At follow-up, we observed significant improvements in glycometabolic, renal and inflammatory profiles (p < 0.001). Proteomic analysis revealed selective changes in key cardiovascular (CV)-related proteins, such as insulin-like growth factor-binding protein 4 (IBP4), thrombospondin-4 (TSP4), intercellular adhesion molecule 1 (ICAM1), and syndecan-4 (SDC4). Conclusions: This study demonstrates significant improvements across multiple CV biomarkers after six months of therapy optimisation in HFimpEF patients, providing evidence for comprehensive therapeutic effects targeting inflammation, oxidative stress, neurohormonal activation, and thrombotic risk. Full article
(This article belongs to the Special Issue Antioxidants in Cardiovascular Medicine: Emerging Trends and Future Perspectives)
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28 pages, 4505 KB  
Article
Resveratrol Mediates Anti-Atherogenic Actions In Vitro and in LDL Receptor-Deficient Mice Fed a High-Fat Diet via Antioxidant, Anti-Inflammatory and Plaque-Stabilising Activities
by Alaa Alahmadi, Reem Alotibi, Yee-Hung Chan, Sarab Taha, Daniah Rifqi, Nouf Alshehri, Sulaiman Alalawi, Fahad Alradi, Alex Gibbs, Timothy R. Hughes and Dipak P. Ramji
Antioxidants 2026, 15(1), 76; https://doi.org/10.3390/antiox15010076 - 7 Jan 2026
Cited by 1 | Viewed by 973
Abstract
Current pharmacotherapies against atherosclerotic cardiovascular disease are associated with considerable residual risk, together with various adverse side effects. Nutraceuticals, such as resveratrol (RSV), with excellent safety profile, represent promising alternatives and potential treatment. However, the full spectrum of anti-atherogenic actions regulated by RSV [...] Read more.
Current pharmacotherapies against atherosclerotic cardiovascular disease are associated with considerable residual risk, together with various adverse side effects. Nutraceuticals, such as resveratrol (RSV), with excellent safety profile, represent promising alternatives and potential treatment. However, the full spectrum of anti-atherogenic actions regulated by RSV and the underlying molecular mechanisms remain poorly understood. The objective of this study therefore was to investigate the impact of RSV on key atherosclerosis-associated processes in monocytes, macrophages, endothelial cells, and smooth muscle cells in vitro, as well as in LDL receptor-deficient mice fed a high-fat diet in vivo. RSV produced beneficial changes in the plasma lipid profile and peripheral blood lymphoid cells in vivo. RSV also attenuated plaque inflammation by decreasing macrophage and T cell content and enhanced markers of plaque stability, with increased levels of smooth muscle cells and collagen content. In vitro, RSV inhibited chemokine-driven monocyte migration, inflammasome activation, matrix metalloproteinase activity, pro-inflammatory gene expression, reactive oxygen species production, and smooth muscle cell invasion. RNA-sequencing of the thoracic aorta revealed key genes and pathways mediating the antioxidant, anti-inflammatory and plaque-stabilising activities of RSV. These studies provide novel mechanistic insights on the anti-atherogenic actions of RSV and support further evaluation in human clinical trials. Full article
(This article belongs to the Special Issue Antioxidants in Cardiovascular Medicine: Emerging Trends and Future Perspectives)
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Review

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25 pages, 1520 KB  
Review
Resveratrol and Redox Regulation in Cardiovascular Disease Across the Life Course: Mechanistic and Translational Perspectives
by Chien-Ning Hsu and You-Lin Tain
Antioxidants 2026, 15(4), 509; https://doi.org/10.3390/antiox15040509 - 20 Apr 2026
Viewed by 494
Abstract
Resveratrol (RSV), a bioactive polyphenol, has emerged as a pleiotropic modulator within the integrated pathophysiology of cardiovascular disease (CVD) across the life course. Effective CVD management requires a transition from organ-centric frameworks to systems-level models that acknowledge dynamic crosstalk among metabolic, renal, and [...] Read more.
Resveratrol (RSV), a bioactive polyphenol, has emerged as a pleiotropic modulator within the integrated pathophysiology of cardiovascular disease (CVD) across the life course. Effective CVD management requires a transition from organ-centric frameworks to systems-level models that acknowledge dynamic crosstalk among metabolic, renal, and cardiovascular networks. Oxidative stress constitutes a central unifying axis in this interconnected biology, propagating cross-organ injury from early developmental stages onward. Mechanistically, RSV acts as a redox-responsive gene regulator by activating the Nrf2–ARE pathway, restoring nitric oxide bioavailability, and orchestrating SIRT1, AMPK, and NF-κB signaling to recalibrate mitochondrial function, inflammatory tone, and endothelial integrity. Within the Developmental Origins of Health and Disease (DOHaD) paradigm, RSV exhibits reprogramming potential that attenuates the intergenerational transmission of hypertension, kidney disease, and metabolic dysfunction. Although clinical translation is constrained by limited bioavailability and rapid metabolism, advanced delivery systems and artificial intelligence-enabled optimization strategies provide promising avenues to enhance therapeutic precision and scalability. This narrative review integrates mechanistic and translational insights to position RSV as a systems-oriented life-course intervention with sustained and intergenerational relevance in CVD. Full article
(This article belongs to the Special Issue Antioxidants in Cardiovascular Medicine: Emerging Trends and Future Perspectives)
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21 pages, 1620 KB  
Review
Polyphenols as Adjuvant Treatment for Heart Failure with Preserved Ejection Fraction (HFpEF): A Review
by Selma Guimarães Ferreira Medeiros, Rita de Cássia Avellaneda Guimarães, Aline Carla Inada, Carolina Di Pietro Fernandes, Rosângela dos Santos Ferreira, Karine de Cássia Freitas, Juliana Rodrigues Donadon, Valter Aragão do Nascimento and Priscila Aiko Hiane
Antioxidants 2026, 15(3), 322; https://doi.org/10.3390/antiox15030322 - 4 Mar 2026
Cited by 1 | Viewed by 904
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome driven by systemic inflammation, persistent oxidative stress, endothelial dysfunction, and impaired mitochondrial bioenergetics. Despite recent therapeutic advances, the management of these specific pathophysiological mechanisms remains a challenge. Polyphenols, bioactive compounds found [...] Read more.
Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome driven by systemic inflammation, persistent oxidative stress, endothelial dysfunction, and impaired mitochondrial bioenergetics. Despite recent therapeutic advances, the management of these specific pathophysiological mechanisms remains a challenge. Polyphenols, bioactive compounds found in plants, have emerged as potential modulators of these pathways. Objective: This review critically summarizes the pathophysiological and molecular evidence supporting the role of polyphenols—specifically phenolic acids, flavonoids, and lignans—in attenuating key pathways implicated in the progression of HFpEF, while also addressing the current limitations in clinical translation. Results: Preclinical evidence indicates that polyphenols regulate cellular homeostasis by activating the Keap1/Nrf2 antioxidant axis and AMPK/SIRT1 metabolic pathways, while inhibiting NF-κB-mediated pro-inflammatory signals and TGF-β fibrotic pathways. These molecular actions collectively preserve endothelial function via PI3K/Akt/eNOS, reduce interstitial fibrosis, and improve myocardial metabolic efficiency. Furthermore, the modulation of gut microbiota amplifies these systemic effects, particularly in obesity-related phenotypes. However, direct clinical application is currently hindered by low bioavailability and a scarcity of randomized trials specifically in HFpEF populations. Polyphenols represent a promising and biologically plausible nutritional therapeutic axis for the multidimensional management of HFpEF. While the molecular rationale is strong, future research should focus on improving bioavailability and conducting high-quality clinical trials to validate efficacy as an adjuvant therapy. Full article
(This article belongs to the Special Issue Antioxidants in Cardiovascular Medicine: Emerging Trends and Future Perspectives)
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23 pages, 1771 KB  
Review
Reactive Nitrogen Species and Fibrinogen: Exploring the Effects of Nitration on Blood Clots
by Francesca Nencini, Serena Borghi, Elvira Giurranna, Ilenia Barbaro, Niccolò Taddei, Claudia Fiorillo and Matteo Becatti
Antioxidants 2025, 14(7), 825; https://doi.org/10.3390/antiox14070825 - 4 Jul 2025
Cited by 3 | Viewed by 2063
Abstract
Reactive nitrogen species (RNS), particularly peroxynitrite (ONOO−), play a central role in post-translational modifications (PTMs) of proteins, including fibrinogen, a key component of the coagulation cascade. This review explores the structural and functional consequences of fibrinogen nitration, with a focus on [...] Read more.
Reactive nitrogen species (RNS), particularly peroxynitrite (ONOO−), play a central role in post-translational modifications (PTMs) of proteins, including fibrinogen, a key component of the coagulation cascade. This review explores the structural and functional consequences of fibrinogen nitration, with a focus on its impact on clot formation, morphology, mechanical stability, and fibrinolysis. Nitration, primarily targeting tyrosine residues within functional domains of the Aα, Bβ, and γ chains, induces conformational changes, dityrosine crosslinking, and aggregation into high molecular weight species. These modifications result in altered fibrin polymerization, the formation of porous and disorganized clot networks, reduced mechanical resilience, and variable susceptibility to fibrinolysis. Moreover, nitrated fibrinogen may affect interactions with platelets and endothelial cells, although current evidence remains limited. Emerging clinical studies support its role as both a prothrombotic mediator and a potential biomarker of oxidative stress in cardiovascular and inflammatory diseases. Finally, we explore both pharmacological interventions, such as NOX inhibitors, and natural antioxidant strategies at counteracting fibrinogen nitration. Overall, fibrinogen nitration emerges as a critical molecular event linking oxidative stress to thrombotic risk. Full article
(This article belongs to the Special Issue Antioxidants in Cardiovascular Medicine: Emerging Trends and Future Perspectives)
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