Oxidative Stress Biomarkers in Cardiovascular Risk and Disease

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 November 2019) | Viewed by 40618

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Guest Editor
Clinical Physiology Institute, National Research Council, 56124 Pisa, Italy

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Guest Editor
Clinical Physiology Institute, National Research Council, 56124 Pisa, Italy

Special Issue Information

Dear Colleagues,

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Western countries. A great amount of evidence indicates that CVD begins in early life with the onset of risk factors that contribute to the development of subclinical atherosclerosis, and subsequently to overt CVD. Thus, primordial, primary prevention, as well as primary and secondary prevention of CVD, are public health priorities.

The evaluation of circulating biomarkers by laboratories is a critical tool to assess antecedent disease (risk of developing a disease), and for screening (for subclinical disease), diagnosis (identify overt disease), disease staging (evaluate disease severity), prognosis (predicting future disease evolution, recurrence and complications), monitoring therapy efficacy and therapy response. Nonetheless, whether the addition of new proposed single biomarkers or multibiomarker panels can provide substantial improvement of traditional risk models is still discussed. Thus, further advances in CV biomarker identification and development remains an important area of research. Among available candidates, oxidative and inflammatory biomarkers are pivotal in the risk and development of CVD. In this context, also gender issues are critical, as gender is known to be associated to differences in many biomarkers, likely related, almost in part, to the presence of estrogen and their antioxidant effects.

Accordingly, we invite investigators to contribute original research articles as well as review articles on following hot topics and debate issues:

  • Oxidative stress biomarker performance: Laboratory pearls and pitfalls
  • Primordial, primary and secondary CVD prevention: Role of oxidative stress
  • Gender-related differences in oxidative stress and their effects on CV prevention and disease
  • Integration of oxidative stress-related biochemical markers and cardioimaging

Dr. Francesca Mastorci
Dr. Alessandro Pingitore
Dr. Cristina Vassalle
Guest Editors

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Keywords

  • cardiovascular prevention and disease
  • circulating biomarkers
  • oxidative stress
  • limits and advantages
  • gender

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Published Papers (5 papers)

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Research

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18 pages, 2878 KiB  
Article
Comparison of Mitochondrial Superoxide Detection Ex Vivo/In Vivo by mitoSOX HPLC Method with Classical Assays in Three Different Animal Models of Oxidative Stress
by Sanela Kalinovic, Matthias Oelze, Swenja Kröller-Schön, Sebastian Steven, Ksenija Vujacic-Mirski, Miroslava Kvandová, Isabella Schmal, Ahmad Al Zuabi, Thomas Münzel and Andreas Daiber
Antioxidants 2019, 8(11), 514; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox8110514 - 28 Oct 2019
Cited by 22 | Viewed by 7257
Abstract
Background: Reactive oxygen and nitrogen species (RONS such as H2O2, nitric oxide) are generated within the organism. Whereas physiological formation rates confer redox regulation of essential cellular functions and provide the basis for adaptive stress responses, their excessive formation [...] Read more.
Background: Reactive oxygen and nitrogen species (RONS such as H2O2, nitric oxide) are generated within the organism. Whereas physiological formation rates confer redox regulation of essential cellular functions and provide the basis for adaptive stress responses, their excessive formation contributes to impaired cellular function or even cell death, organ dysfunction and severe disease phenotypes of the entire organism. Therefore, quantification of RONS formation and knowledge of their tissue/cell/compartment-specific distribution is of great biological and clinical importance. Methods: Here, we used a high-performance/pressure liquid chromatography (HPLC) assay to quantify the superoxide-specific oxidation product of the mitochondria-targeted fluorescence dye triphenylphosphonium-linked hydroethidium (mitoSOX) in biochemical systems and three animal models with established oxidative stress. Type 1 diabetes (single injection of streptozotocin), hypertension (infusion of angiotensin-II for 7 days) and nitrate tolerance (infusion of nitroglycerin for 4 days) was induced in male Wistar rats. Results: The usefulness of mitoSOX/HPLC for quantification of mitochondrial superoxide was confirmed by xanthine oxidase activity as well as isolated stimulated rat heart mitochondria in the presence or absence of superoxide scavengers. Vascular function was assessed by isometric tension methodology and was impaired in the rat models of oxidative stress. Vascular dysfunction correlated with increased mitoSOX oxidation but also classical RONS detection assays as well as typical markers of oxidative stress. Conclusion: mitoSOX/HPLC represents a valid method for detection of mitochondrial superoxide formation in tissues of different animal disease models and correlates well with functional parameters and other markers of oxidative stress. Full article
(This article belongs to the Special Issue Oxidative Stress Biomarkers in Cardiovascular Risk and Disease)
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15 pages, 4041 KiB  
Article
Endothelin-1-Induced Microvascular ROS and Contractility in Angiotensin-II-Infused Mice Depend on COX and TP Receptors
by Christopher S. Wilcox, Cheng Wang and Dan Wang
Antioxidants 2019, 8(6), 193; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox8060193 - 22 Jun 2019
Cited by 17 | Viewed by 4835
Abstract
(1) Background: Angiotensin II (Ang II) and endothelin 1 (ET-1) generate reactive oxygen species (ROS) that can activate cyclooxygenase (COX). However, thromboxane prostanoid receptors (TPRs) are required to increase systemic markers of ROS during Ang II infusion in mice. We hypothesized that COX [...] Read more.
(1) Background: Angiotensin II (Ang II) and endothelin 1 (ET-1) generate reactive oxygen species (ROS) that can activate cyclooxygenase (COX). However, thromboxane prostanoid receptors (TPRs) are required to increase systemic markers of ROS during Ang II infusion in mice. We hypothesized that COX and TPRs are upstream requirements for the generation of vascular ROS by ET-1. (2) Methods: ET-1-induced vascular contractions and ROS were assessed in mesenteric arterioles from wild type (+/+) and knockout (−/−) of COX1 or TPR mice infused with Ang II (400 ng/kg/min × 14 days) or a vehicle. (3) Results: Ang II infusion appeared to increase microvascular protein expression of endothelin type A receptors (ETARs), TPRs, and COX1 and 2 in COX1 and TPR +/+ mice but not in −/− mice. Ang II infusion increased ET-1-induced vascular contractions and ROS, which were prevented by a blockade of COX1 and 2 in TPR −/− mice. ET-1 increased the activity of aortic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and decreased superoxide dismutase (SOD) 1, 2, and 3 in Ang-II-infused mice, which were prevented by a blockade of TPRs. (4) Conclusion: Activation of vascular TPRs by COX products are required for ET-1 to increase vascular contractions and ROS generation from NADPH oxidase and reduce ROS metabolism by SOD. These effects require an increase in these systems by prior infusion of Ang II. Full article
(This article belongs to the Special Issue Oxidative Stress Biomarkers in Cardiovascular Risk and Disease)
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12 pages, 1119 KiB  
Article
Emerging Biomarkers of Oxidative Stress in Acute and Stable Coronary Artery Disease: Levels and Determinants
by Valter Lubrano, Alessandro Pingitore, Irene Traghella, Simona Storti, Serena Parri, Sergio Berti, Rudina Ndreu, Andrea Andrenelli, Cataldo Palmieri, Giorgio Iervasi, Francesca Mastorci and Cristina Vassalle
Antioxidants 2019, 8(5), 115; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox8050115 - 01 May 2019
Cited by 23 | Viewed by 4818
Abstract
Background: Oxidative stress is crucial in the pathogenesis of atherosclerosis and acute myocardial infarction (AMI). Under the generic terms “oxidative stress” (OS), many biomarkers belonging to different pathways have been proposed. Aim: To compare the levels of recently proposed OS-related parameters in acute [...] Read more.
Background: Oxidative stress is crucial in the pathogenesis of atherosclerosis and acute myocardial infarction (AMI). Under the generic terms “oxidative stress” (OS), many biomarkers belonging to different pathways have been proposed. Aim: To compare the levels of recently proposed OS-related parameters in acute coronary syndromes (ACS) and stable coronary artery disease (CAD), to evaluate their effectiveness as additive risk or illness indicators of stable and acute ischemic events, and their response over time during the course of AMI. Methods: 76 ACS, 77 CAD patients, and 63 controls were enrolled in the study. Different OS-related biomarkers, including reactive oxygen metabolites (ROM), the total antioxidant capacity (OXY), nitrite/nitrate (final nitric oxide products, NOx), and Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), were evaluated. Moreover, time response during AMI course (admission, and 6, 12, 18, 24, 36, and 48 hours after, T0-T6, respectively) and correlation with traditional cardiovascular (CV) risk factors (age, gender, hypertension, diabetes mellitus, dyslipidemia, smoking habit) were also assessed. Results: Over time, ROM progressively increased while OXY and NOx decreased. Kinetics of LOX-1 during AMI shows that this biomarker boosts early during the acute event (T1 and T2) and then progressively decreases, being significantly lower from T0 to T6. Different OS-related biomarkers were differentially associated with CV risk factors and CAD or ACS presence. Conclusion: Differences in OS-related biomarkers (between groups, according to the response over time during AMI, and to the presence of CV risk factors) confirmed OS involvement in the transition from healthy status to stable CAD and ACS, although evidencing the heterogeneous nature of redox processes. In future, a multi-marker panel including different biomarkers and pathways of oxidative stress could be evaluated as an additive tool to be used in the CV prevention, diagnosis, patient stratification, and treatment. Full article
(This article belongs to the Special Issue Oxidative Stress Biomarkers in Cardiovascular Risk and Disease)
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13 pages, 2152 KiB  
Article
Analysis of Protein Oxidative Modifications in Follicular Fluid from Fertile Women: Natural Versus Stimulated Cycles
by Irantzu Pérez-Ruiz, Susana Meijide, María-Luisa Hérnandez, Rosaura Navarro, Zaloa Larreategui, Marcos Ferrando, María-Begoña Ruiz-Larrea and José-Ignacio Ruiz-Sanz
Antioxidants 2018, 7(12), 176; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox7120176 - 27 Nov 2018
Cited by 3 | Viewed by 4028
Abstract
Oxidative stress is associated with obstetric complications during ovarian hyperstimulation in women undergoing in vitro fertilization. The follicular fluid contains high levels of proteins, which are the main targets of free radicals. The aim of this work was to determine specific biomarkers of [...] Read more.
Oxidative stress is associated with obstetric complications during ovarian hyperstimulation in women undergoing in vitro fertilization. The follicular fluid contains high levels of proteins, which are the main targets of free radicals. The aim of this work was to determine specific biomarkers of non-enzymatic oxidative modifications of proteins from follicular fluid in vivo, and the effect of ovarian stimulation with gonadotropins on these biomarkers. For this purpose, 27 fertile women underwent both a natural and a stimulated cycle. The biomarkers, glutamic semialdehyde (GSA), aminoadipic semialdehyde (AASA), Nε-(carboxymethyl)lysine (CML), and Nε-(carboxyethyl)lysine (CEL), were measured by gas-liquid chromatography coupled to mass spectrometry. Results showed that follicular fluid contained products of protein modifications by direct metal-catalyzed oxidation (GSA and AASA), glycoxidation (CML and CEL), and lipoxidation (CML). GSA was the most abundant biomarker (91.5%). The levels of CML amounted to 6% of the total lesions and were higher than AASA (1.3%) and CEL (1.2%). In the natural cycle, CEL was significantly lower (p < 0.05) than in the stimulated cycle, suggesting that natural cycles are more protected against protein glycoxidation. These findings are the basis for further research to elucidate the possible relevance of this follicular biomarker of advanced glycation end product in fertility programs. Full article
(This article belongs to the Special Issue Oxidative Stress Biomarkers in Cardiovascular Risk and Disease)
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Review

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28 pages, 3916 KiB  
Review
Measurement and Clinical Significance of Lipid Peroxidation as a Biomarker of Oxidative Stress: Oxidative Stress in Diabetes, Atherosclerosis, and Chronic Inflammation
by Fumiaki Ito, Yoko Sono and Tomoyuki Ito
Antioxidants 2019, 8(3), 72; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox8030072 - 25 Mar 2019
Cited by 296 | Viewed by 19127
Abstract
Endothelial dysfunction is one of the initial steps in the pathogenesis of atherosclerosis and development of cardiovascular disease in patients with diabetes mellitus. Several risk factors are associated with endothelial dysfunction and atherosclerosis, such as hypertension, dyslipidaemia, inflammation, oxidative stress, and advanced glycation-end [...] Read more.
Endothelial dysfunction is one of the initial steps in the pathogenesis of atherosclerosis and development of cardiovascular disease in patients with diabetes mellitus. Several risk factors are associated with endothelial dysfunction and atherosclerosis, such as hypertension, dyslipidaemia, inflammation, oxidative stress, and advanced glycation-end products. Among these risk factors, oxidative stress is the largest contributor to the formation of atherosclerotic plaques. Measurement of reactive oxygen species (ROS) is still difficult, and assays for the measurement of ROS have failed to show a consistent correlation between pathological states and oxidative stress. To solve this problem, this review summarizes the current knowledge on biomarkers of oxidative stress, especially lipid peroxidation, and discusses the roles of oxidative stress, as measured by indices of lipid peroxidation, in diabetes mellitus, atherosclerosis, and chronic inflammation. Full article
(This article belongs to the Special Issue Oxidative Stress Biomarkers in Cardiovascular Risk and Disease)
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