Submit to Antioxidants Review for Antioxidants Propose a Special Issue

Journal Browser

Oxidative Stress in Cardiovascular Disease and Comorbidities

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Published Papers

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 2022) | Viewed by 26290

Share This Special Issue

Special Issue Editors

Prof. Dr. Guillermo Zalba

E-Mail Website
Guest Editor

Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain
Interests: oxidative stress; hypertension; atherosclerosis; metabolic disorders; NADPH oxidases; telomere
Special Issues, Collections and Topics in MDPI journals

Dr. María U. Moreno Zulategui

E-Mail Website
Guest Editor

1. Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain
2. Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain
3. Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain
Interests: oxidative stress; cardiovascular diseases; heart failure; hypertension; myocardial fibrosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiovascular diseases and their related comorbidities (obesity, diabetes, kidney disease, dyslipidemia) are the main cause of morbidity and mortality worldwide. This is expected to worsen, as the population ages and the prevalence of their risk factors increases. In many areas, early diagnosis is not available and current therapies lack specificity or are not adequately effective. Therefore, cardiovascular diseases remain a major unmet medical need and a relevant area of research.

The molecular mechanisms underlying cardiovascular diseases are complex and affect multiple cell types. However, damage by oxidative stress and subsequent alterations seem to be relevant common mechanisms in cardiovascular disease.

We invite you to submit your latest research findings or a review to this Special Issue, which aims to bring together up-to-date knowledge on the importance of oxidative stress and reactive oxygen species (ROS) as mediators and targets in cardiovascular and related diseases. We welcome submissions on cardiac and vascular damage by ROS, as well as the influence of risk factors such as age, obesity, diabetes, and renal disease. Sources of ROS are diverse and interconnected, and all are relevant, although NADPH oxidases stand out as potential therapeutic targets, since novel, specific inhibitors are being developed. In addition, the interplay of diverse cell types is of special interest since ROS may have effects on cells different from their origin. State-of-the-art genomics and proteomic approaches that provide more complete evaluation of processes are welcome. Research with high translational potential, such as that which includes biomarkers, is of interest.

With your collaboration, we aim to provide the scientific community with state-of-the-art information on mechanisms and targets that may help to reduce the burden of cardiovascular disease. We look forward to your contribution and will be happy to discuss your suggestions.

Prof. Dr. Guillermo Zalba
Dr. María U. Moreno Zulategui
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. 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.

Published Papers (11 papers)

Download All Papers

Editorial

Jump to: Research, Review

3 pages, 201 KiB

Open AccessEditorial

Oxidative Stress in Cardiovascular Disease and Comorbidities

by Guillermo Zalba and María U. Moreno

Antioxidants 2022, 11(8), 1519; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11081519 - 03 Aug 2022

Cited by 2 | Viewed by 1253

Abstract

Reactive oxygen species (ROS), both as second messengers and as contributors to oxidative stress, play a major, complex role in the initiation, development and outcomes of cardiovascular diseases [...] Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease and Comorbidities)

Research

Jump to: Editorial, Review

14 pages, 1153 KiB

Open AccessArticle

Myeloperoxidase as a Potential Biomarker of Acute-Myocardial-Infarction-Induced Depression and Suppression of the Innate Immune System

by Andreas Baranyi, Dietmar Enko, Andreas Meinitzer, Dirk Von Lewinski, Hans-Bernd Rothenhäusler, Leonhard Harpf, Heimo Traninger, Barbara Obermayer-Pietsch, Birgit M. Harb, Melanie Schweinzer, Moritz Platzer and Sieglinde Zelzer

Antioxidants 2022, 11(11), 2083; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11112083 - 22 Oct 2022

Cited by 1 | Viewed by 1419

Abstract

While myeloperoxidase (MPO) serves as an indicator of both neutrophil and innate-immune-system function, the potential suppression of the innate immune system in patients with acute myocardial infarction (AMI)-induced depression might be evidenced by a decrease in MPO serum levels. The aim of this prospective study was to (1) determine whether serum concentrations of MPO vary immediately and 6 months after AMI and (2) to investigate whether MPO concentrations at the time of the AMI are significant predictors of AMI-induced depression and the depression-associated suppression of the innate immune system. A total of 109 AMI patients were assessed with the Hamilton Depression Scale (HAMD-17) immediately after admission to the hospital and 6 months later. The MPO status was assessed with serum samples, which were also collected immediately and 6 months after AMI. The depressive patients showed significantly lower MPO blood levels immediately and 6 months after the AMI compared to the patients without depression (ANCOVA: MPO (depression) F = 4.764, df = 1, p = 0.031). The baseline MPO was observed as a significant predictor (p = 0.027) of AMI-induced depression 6 months after AMI. MPO is a potential biomarker for AMI-induced depression, indicating a depression-associated suppression of the innate immune system. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease and Comorbidities)

► Show Figures

Figure 1

16 pages, 318 KiB

Open AccessArticle

The Association of Oxidative and Antioxidant Potential with Cardiometabolic Risk Profile in the Group of 60- to 65-Year-Old Seniors from Central Poland

by Bartłomiej K. Sołtysik, Kamil Karolczak, Cezary Watała and Tomasz Kostka

Antioxidants 2022, 11(6), 1065; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11061065 - 27 May 2022

Cited by 4 | Viewed by 1376

Abstract

Pathogenesis of cardiovascular diseases is caused by, inter alia, oxidative stress. On the other hand, cardiovascular risk factors may cause redox imbalance. The pathological pathways between those components are to be determined. In the group comprised of 300 sex-matched subjects, we evaluated a number of cardiovascular risk factors: blood pressure, body mass, lipids, glucose, homocysteine, uric acid, von Willebrand factor (vWF), VCAM-1 and ICAM-1. The presence of cardiovascular diseases and drugs for their treatment were examined. Secondly, we assessed total antioxidative status (TAS), total oxidative status (TOS) and other markers of oxidative stress. TAS was inversely related to LDL cholesterol. TOS was positively associated with BMI and female sex, but negatively associated with the use of angiotensin II receptor antagonists. Plasma lipid peroxides concentration was positively related to ICAM-1 and presence of stroke, whereas platelet lipid peroxides were positively associated with vWF. Platelets proteins thiol groups were in a positive relationship with vWF, but in a negative relationship with uric acid and diagnosed lipid disorders. Both free thiol and amino groups were positively associated with plasma glucose. Platelets free amino groups were related to platelets count. Superoxide generation by blood platelets (both with and without homocysteine) was positively connected to glucose level. Among women, oxidative markers appear to be more related to glucose level, whereas among men they are related to body mass indices. TAS, TOS and oxidative markers are largely related to modifiable cardiovascular risk factors such as body mass, and intake of drugs such as angiotensin II receptor blockers. Plasma and platelet oxidation markers appear to be especially associated with glucose concentration. The presented analyses unanimously indicate strong connections between cardiovascular risk factors and redox potential and specify how cardiometabolic interventions may counter-balance oxidative stress. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease and Comorbidities)

15 pages, 2741 KiB

Open AccessArticle

Human Lysyl Oxidase Over-Expression Enhances Baseline Cardiac Oxidative Stress but Does Not Aggravate ROS Generation or Infarct Size Following Myocardial Ischemia-Reperfusion

by Laura Valls-Lacalle, Lídia Puertas-Umbert, Saray Varona, José Martínez-González, Cristina Rodríguez and Antonio Rodríguez-Sinovas

Antioxidants 2022, 11(1), 75; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11010075 - 29 Dec 2021

Cited by 4 | Viewed by 1635

Abstract

Lysyl oxidase (LOX) is an enzyme critically involved in collagen maturation, whose activity releases H₂O₂ as a by-product. Previous studies demonstrated that LOX over-expression enhances reactive oxygen species (ROS) production and exacerbates cardiac remodeling induced by pressure overload. However, whether LOX influences acute myocardial infarction and post-infarct left ventricular remodeling and the contribution of LOX to myocardial oxidative stress following ischemia-reperfusion have not been analyzed. Isolated hearts from transgenic mice over-expressing human LOX in the heart (TgLOX) and wild-type (WT) littermates were subjected to global ischemia and reperfusion. Although under basal conditions LOX transgenesis is associated with higher cardiac superoxide levels than WT mice, no differences in ROS production were detected in ischemic hearts and a comparable acute ischemia-reperfusion injury was observed (infarct size: 56.24 ± 9.44 vs. 48.63 ± 2.99% of cardiac weight in WT and TgLOX, respectively). Further, similar changes in cardiac dimensions and function were observed in TgLOX and WT mice 28 days after myocardial infarction induced by transient left anterior descending (LAD) coronary artery occlusion, and no differences in scar area were detected (20.29 ± 3.10 vs. 21.83 ± 2.83% of left ventricle). Our data evidence that, although LOX transgenesis induces baseline myocardial oxidative stress, neither ROS production, infarct size, nor post-infarction cardiac remodeling were exacerbated following myocardial ischemia-reperfusion. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease and Comorbidities)

► Show Figures

Figure 1

19 pages, 3801 KiB

Open AccessArticle

Endothelial NOX5 Expression Modulates Thermogenesis and Lipolysis in Mice Fed with a High-Fat Diet and 3T3-L1 Adipocytes through an Interleukin-6 Dependent Mechanism

by Jorge G. García, Carlos de Miguel, Fermín I. Milagro, Guillermo Zalba and Eduardo Ansorena

Antioxidants 2022, 11(1), 30; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11010030 - 24 Dec 2021

Cited by 8 | Viewed by 2978

Abstract

Obesity is a global health issue associated with the development of metabolic syndrome, which correlates with insulin resistance, altered lipid homeostasis, and other pathologies. One of the mechanisms involved in the development of these pathologies is the increased production of reactive oxygen species (ROS). One of the main producers of ROS is the family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, among which NOX5 is the most recently discovered member. The aim of the present work is to describe the effect of endothelial NOX5 expression on neighboring adipose tissue in obesity conditions by using two systems. An in vivo model based on NOX5 conditional knock-in mice fed with a high-fat diet and an in vitro model developed with 3T3-L1 adipocytes cultured with conditioned media of endothelial NOX5-expressing bEnd.3 cells, previously treated with glucose and palmitic acid. Endothelial NOX5 expression promoted the expression and activation of specific markers of thermogenesis and lipolysis in the mesenteric and epididymal fat of those mice fed with a high-fat diet. Additionally, the activation of these processes was derived from an increase in IL-6 production as a result of NOX5 activity. Accordingly, 3T3-L1 adipocytes treated with conditioned media of endothelial NOX5-expressing cells, presented higher expression of thermogenic and lipolytic genes. Moreover, endothelial NOX5-expressing bEnd.3 cells previously treated with glucose and palmitic acid also showed interleukin (IL-6) production. Finally, it seems that the increase in IL-6 stimulated the activation of markers of thermogenesis and lipolysis through phosphorylation of STAT3 and AMPK, respectively. In conclusion, in response to obesogenic conditions, endothelial NOX5 activity could promote thermogenesis and lipolysis in the adipose tissue by regulating IL-6 production. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease and Comorbidities)

► Show Figures

Figure 1

14 pages, 3665 KiB

Open AccessArticle

Relationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts

by Estefanía Tarazón, Lorena Pérez-Carrillo, Isaac Giménez-Escamilla, Pablo Ramos-Castellanos, Luis Martínez-Dolz, Manuel Portolés and Esther Roselló-Lletí

Antioxidants 2021, 10(11), 1750; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10111750 - 01 Nov 2021

Cited by 5 | Viewed by 2725

Abstract

Although the roles of telomeres and oxidative stress in ischaemic cardiomyopathy (ICM) are known, mechanisms of telomere homeostasis and their relationship with oxidative stress are incompletely understood. We performed two RNA-seq analyses (mRNA n = 23; ncRNA n = 30) and protein validation on left ventricles of explanted hearts from ICM and control subjects. We observed dysregulation of the shelterin and cohesin complexes, which was related to an increase in the response to cellular oxidative stress. Moreover, we found alterations at mRNA level in the mechanisms of telomeric DNA repair. Specifically, increased RAD51D mRNA levels were correlated with left ventricular diameters. RAD51D protein levels were unaltered, however, and were inversely corelated with the miR-103a-3p upregulation. We also observed the overexpression of lncRNAs (TERRA and GUARDIN) involved in telomere protection in response to stress and alterations in their regulatory molecules. Expression of the TERRA transcription factor ATF7 was correlated with superoxide dismutase 1 expression and left ventricular diameters. The levels of GUARDIN and its transcription factor FOSL2 were correlated with those of catalase. Therefore, we showed specific alterations in the mechanisms of telomeric DNA repair and protection, and these alterations are related to an increase in the response mechanisms to oxidative stress and cardiac dysfunction in ICM. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease and Comorbidities)

► Show Figures

Graphical abstract

15 pages, 1629 KiB

Open AccessArticle

CRIF1 Deficiency Increased Homocysteine Production by Disrupting Dihydrofolate Reductase Expression in Vascular Endothelial Cells

by Ikjun Lee, Shuyu Piao, Seonhee Kim, Harsha Nagar, Su-Jeong Choi, Byeong Hwa Jeon, Sang-Ha Oh, Kaikobad Irani and Cuk-Seong Kim

Antioxidants 2021, 10(11), 1645; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10111645 - 20 Oct 2021

Cited by 3 | Viewed by 1669

Abstract

Elevated plasma homocysteine levels can induce vascular endothelial dysfunction; however, the mechanisms regulating homocysteine metabolism in impaired endothelial cells are currently unclear. In this study, we deleted the essential mitoribosomal gene CR6 interacting factor 1 (CRIF1) in human umbilical vein endothelial cells (HUVECs) and mice to induce endothelial cell dysfunction; then, we monitored homocysteine accumulation. We found that CRIF1 downregulation caused significant increases in intracellular and plasma concentrations of homocysteine, which were associated with decreased levels of folate cycle intermediates such as 5-methyltetrahydrofolate (MTHF) and tetrahydrofolate (THF). Moreover, dihydrofolate reductase (DHFR), a key enzyme in folate-mediated metabolism, exhibited impaired activity and decreased protein expression in CRIF1 knockdown endothelial cells. Supplementation with folic acid did not restore DHFR expression levels or MTHF and homocysteine concentrations in endothelial cells with a CRIF1 deletion or DHFR knockdown. However, the overexpression of DHFR in CRIF1 knockdown endothelial cells resulted in decreased accumulation of homocysteine. Taken together, our findings suggest that CRIF1-deleted endothelial cells accumulated more homocysteine, compared with control cells; this was primarily mediated by the disruption of DHFR expression. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease and Comorbidities)

► Show Figures

Figure 1

17 pages, 2986 KiB

Open AccessArticle

Expression of Endothelial NOX5 Alters the Integrity of the Blood-Brain Barrier and Causes Loss of Memory in Aging Mice

by Adriana Cortés, Maite Solas, Álvaro Pejenaute, Miguel A. Abellanas, Marcos Garcia-Lacarte, Maria S. Aymerich, Javier Marqués, María J. Ramírez and Guillermo Zalba

Antioxidants 2021, 10(8), 1311; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10081311 - 20 Aug 2021

Cited by 12 | Viewed by 2382

Abstract

Blood-Brain barrier (BBB) disruption is a hallmark of central nervous system (CNS) dysfunction, and oxidative stress is one of the molecular mechanisms that may underlie this process. NADPH oxidases (NOX) are involved in oxidative stress-mediated vascular dysfunction and participate in the pathophysiology of its target organs. The NADPH oxidase 5 (NOX5) isoform is absent in rodents, and although little is known about the role it may play in disrupting the BBB, it has recently been implicated in experimental stroke. Our aim was to investigate the role of NADPH oxidase 5 (NOX5) in promoting vascular alterations and to identify its impact on the cognitive status of aged mice. No differences were detected in the arterial blood pressure or body weight between knock-in mice expressing endothelial NOX5 and the control mice. The Morris water maze test showed memory impairments in the aged knock-in mice expressing NOX5 compared with their control littermates. For assessing the BBB integrity, we studied the protein expression of two tight junction (TJ) proteins: Zonula occludens-1 (ZO-1) and occludin. Compared to the control animals, Aged NOX5 mice exhibited reduced levels of both proteins, demonstrating an alteration of the BBB integrity. Our data indicate that vascular NOX5 may favor behavioral changes with aging through oxidative stress-mediated BBB breakdown. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease and Comorbidities)

► Show Figures

Figure 1

16 pages, 9725 KiB

Open AccessArticle

Oxidative Stress and Inflammatory Markers in Abdominal Aortic Aneurysm

by David Sánchez-Infantes, Meritxell Nus, Miquel Navas-Madroñal, Joan Fité, Belén Pérez, Antonio J. Barros-Membrilla, Begoña Soto, José Martínez-González, Mercedes Camacho, Cristina Rodriguez, Ziad Mallat and María Galán

Antioxidants 2021, 10(4), 602; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10040602 - 14 Apr 2021

Cited by 36 | Viewed by 3822

Abstract

Abdominal aortic aneurysm (AAA) is increasing due to aging of the population and is a major cause of death among the elderly. Ultrasound screening programs are useful in early diagnosis, but aneurysm size is not always a good predictor of rupture. Our aim was to analyze the value of circulating molecules related to oxidative stress and inflammation as new biomarkers to assist the management of AAA. The markers were quantified by ELISA, and their expression in the aneurysmal wall was studied by real-time PCR and by immunostaining. Correlation analysis of the studied markers with aneurysm diameter and peak wall stress (PWS), obtained by finite element analysis, and multivariate regression analysis to assess potential confounding factors were performed. Our study shows an extensive inflammatory infiltration in the aneurysmal wall, mainly composed by T-cells, macrophages and B-cells and altered levels of reactive oxygen species (ROS), IgM, IgG, CD38, GDF15, S100A4 and CD36 in plasma and in the aneurysmal tissue of AAA patients compared with controls. Circulating levels of IgG, CD38 and GDF15 positively correlated with abdominal aortic diameter, and CD38 was correlated with PWS. Our data show that altered levels of IgG, CD38 and GDF15 have potential diagnostic value in the assessment of AAA. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease and Comorbidities)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

18 pages, 1972 KiB

Open AccessReview

Antioxidants in Arrhythmia Treatment—Still a Controversy? A Review of Selected Clinical and Laboratory Research

by Jakub Szyller, Dariusz Jagielski and Iwona Bil-Lula

Antioxidants 2022, 11(6), 1109; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11061109 - 02 Jun 2022

Cited by 12 | Viewed by 4134

Abstract

Antioxidants are substances that can prevent damage to cells caused by free radicals. Production of reactive oxygen species and the presence of oxidative stress play an important role in cardiac arrhythmias. Currently used antiarrhythmic drugs have many side effects. The research on animals and humans using antioxidants (such as vitamins C and E, resveratrol and synthetic substances) yields many interesting but inconclusive results. Natural antioxidants, such as vitamins C and E, can reduce the recurrence of atrial fibrillation (AF) after successful electrical cardioversion and protect against AF after cardiac surgery, but do not affect the incidence of atrial arrhythmias in critically ill patients with trauma. Vitamins C and E may also effectively treat ventricular tachycardia, ventricular fibrillation and long QT-related arrhythmias. Another natural antioxidant—resveratrol—may effectively treat AF and ventricular arrhythmias caused by ischaemia–reperfusion injury. It reduces the mortality associated with life-threatening ventricular arrhythmias and can be used to prevent myocardial remodelling. Statins also show antioxidant activity. Their action is related to the reduction of oxidative stress and anti-inflammatory effect. Therefore, statins can reduce the post-operative risk of AF and may be useful in lowering its recurrence rate after successful cardioversion. Promising results also apply to polyphenols, nitric oxide synthase inhibitors and MitoTEMPO. Although few clinical trials have been conducted, the use of antioxidants in treating arrhythmias is an interesting prospect. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease and Comorbidities)

► Show Figures

Figure 1

19 pages, 678 KiB

Open AccessReview

Legacy in Cardiovascular Risk Factors Control: From Theory to Future Therapeutic Strategies?

by Lucie Pothen and Jean-Luc Balligand

Antioxidants 2021, 10(11), 1849; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10111849 - 22 Nov 2021

Cited by 3 | Viewed by 1759

Abstract

In medicine, a legacy effect is defined as the sustained beneficial effect of a given treatment on disease outcomes, even after cessation of the intervention. Initially described in optimized control of diabetes, it was also observed in clinical trials exploring intensification strategies for other cardiovascular risk factors, such as hypertension or hypercholesterolemia. Mechanisms of legacy were particularly deciphered in diabetes, leading to the concept of metabolic memory. In a more discreet manner, other memory phenomena were also described in preclinical studies that demonstrated long-lasting deleterious effects of lipids or angiotensin II on vascular wall components. Interestingly, epigenetic changes and reactive oxygen species (ROS) appear to be common features of “memory” of the vascular wall. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease and Comorbidities)

► Show Figures