Oxidative Stress and Atherosclerosis

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 2023) | Viewed by 11744

Special Issue Editors


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Guest Editor
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, 00161 Rome, Italy
Interests: NADPH oxidase; endothelial dysfunction; atherosclerosis

Special Issue Information

Dear Colleague,

Atherosclerotic complications are an expression of several cardiovascular diseases, such as myocardial infarction, stroke and peripheral arterial disease, and these diseases are the main cause of morbidity and mortality in Western countries. Oxidative stress plays a pivotal role in this pathological process. Several enzymes that produce reactive oxidant species (ROS), such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, myeloperoxidase (MPO) and uncoupled nitric oxide synthase (NOS), determine a pro-inflammatory status, which causes the formation of atherosclerosis through endothelial dysfunction, oxidation of LDL, reduction in the antioxidant state and a greater tendency to the prothrombotic state.

This Special Issue aims to analyze the role of oxidative stress in classic cardiovascular risk factors (hypertension, diabetes mellitus, cigarette smoking, obesity and dyslipidemia) and in proven atherosclerotic diseases (peripheral arterial disease, coronary artery disease and stroke). Furthermore, we intend to collect papers which discuss the pathophysiological mechanisms of atherosclerosis and evaluate any antioxidant treatments that can potentially reduce atherosclerotic complications. 

Prof. Dr. Lorenzo Loffredo
Prof. Dr. Roberto Carnevale
Guest Editors

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Keywords

  • oxidative stress
  • NADPH oxidase
  • endothelial dysfunction
  • platelet aggregation
  • antioxidant treatment
  • autophagy

Published Papers (5 papers)

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Research

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19 pages, 7894 KiB  
Article
Lysyl Oxidase in Ectopic Cardiovascular Calcification: Role of Oxidative Stress
by Carme Ballester-Servera, Judith Alonso, Laia Cañes, Paula Vázquez-Sufuentes, Ana B. García-Redondo, Cristina Rodríguez and José Martínez-González
Antioxidants 2024, 13(5), 523; https://doi.org/10.3390/antiox13050523 - 26 Apr 2024
Viewed by 2141
Abstract
Lysyl oxidase (LOX)-mediated extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease; however, this enzyme also induces oxidative stress. We addressed the contribution of LOX-dependent oxidative stress to cardiovascular calcification. LOX is upregulated in human-calcified atherosclerotic lesions and atheromas from atherosclerosis-challenged [...] Read more.
Lysyl oxidase (LOX)-mediated extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease; however, this enzyme also induces oxidative stress. We addressed the contribution of LOX-dependent oxidative stress to cardiovascular calcification. LOX is upregulated in human-calcified atherosclerotic lesions and atheromas from atherosclerosis-challenged LOX transgenic mice (TgLOXVSMC) and colocalized with a marker of oxidative stress (8-oxo-deoxyguanosine) in vascular smooth muscle cells (VSMCs). Similarly, in calcific aortic valves, high LOX expression was detected in valvular interstitial cells (VICs) positive for 8-oxo-deoxyguanosine, while LOX and LOXL2 expression correlated with osteogenic markers (SPP1 and RUNX2) and NOX2. In human VICs, mito-TEMPO and TEMPOL attenuated the increase in superoxide anion levels and the mineralization induced by osteogenic media (OM). Likewise, in OM-exposed VICs, β-aminopropionitrile (a LOX inhibitor) ameliorated both oxidative stress and calcification. Gain- and loss-of-function approaches in VICs demonstrated that while LOX silencing negatively modulates oxidative stress and calcification induced by OM, lentiviral LOX overexpression exacerbated oxidative stress and VIC calcification, effects that were prevented by mito-TEMPO, TEMPOL, and β-aminopropionitrile. Our data indicate that LOX-induced oxidative stress participates in the procalcifying effects of LOX activity in ectopic cardiovascular calcification, and highlight the multifaceted role played by LOX isoenzymes in cardiovascular diseases. Full article
(This article belongs to the Special Issue Oxidative Stress and Atherosclerosis)
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19 pages, 5013 KiB  
Article
CORM-A1 Alleviates Pro-Atherogenic Manifestations via miR-34a-5p Downregulation and an Improved Mitochondrial Function
by Hitarthi S. Vyas, Ravirajsinh N. Jadeja, Aliasgar Vohra, Kapil K. Upadhyay, Menaka C. Thounaojam, Manuela Bartoli and Ranjitsinh V. Devkar
Antioxidants 2023, 12(5), 997; https://doi.org/10.3390/antiox12050997 - 25 Apr 2023
Cited by 3 | Viewed by 1575
Abstract
Atherogenesis involves multiple cell types undergoing robust metabolic processes resulting in mitochondrial dysfunction, elevated reactive oxygen species (ROS), and consequent oxidative stress. Carbon monoxide (CO) has been recently explored for its anti-atherogenic potency; however, the effects of CO on ROS generation and mitochondrial [...] Read more.
Atherogenesis involves multiple cell types undergoing robust metabolic processes resulting in mitochondrial dysfunction, elevated reactive oxygen species (ROS), and consequent oxidative stress. Carbon monoxide (CO) has been recently explored for its anti-atherogenic potency; however, the effects of CO on ROS generation and mitochondrial dysfunction in atherosclerosis remain unexplored. Herein, we describe the anti-atherogenic efficacy of CORM-A1, a CO donor, in in vitro (ox-LDL-treated HUVEC and MDMs) and in vivo (atherogenic diet-fed SD rats) experimental models. In agreement with previous data, we observed elevated miR-34a-5p levels in all our atherogenic model systems. Administration of CO via CORM-A1 accounted for positive alterations in the expression of miR-34a-5p and transcription factors/inhibitors (P53, NF-κB, ZEB1, SNAI1, and STAT3) and DNA methylation pattern, thereby lowering its countenance in atherogenic milieu. Inhibition of miR-34a-5p expression resulted in restoration of SIRT-1 levels and of mitochondrial biogenesis. CORM-A1 supplementation further accounted for improvement in cellular and mitochondrial antioxidant capacity and subsequent reduction in ROS. Further and most importantly, CORM-A1 restored cellular energetics by improving overall cellular respiration in HUVECs, as evidenced by restored OCR and ECAR rates, whereas a shift from non-mitochondrial to mitochondrial respiration was observed in atherogenic MDMs, evidenced by unaltered glycolytic respiration and maximizing OCR. In agreement with these results, CORM-A1 treatment also accounted for elevated ATP production in both in vivo and in vitro experimental models. Cumulatively, our studies demonstrate for the first time the mechanism of CORM-A1-mediated amelioration of pro-atherogenic manifestations through inhibition of miR-34a-5p expression in the atherogenic milieu and consequential rescue of SIRT1-mediated mitochondrial biogenesis and respiration. Full article
(This article belongs to the Special Issue Oxidative Stress and Atherosclerosis)
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15 pages, 3248 KiB  
Article
Interleukin-33 Induces Neutrophil Extracellular Trap (NET) Formation and Macrophage Necroptosis via Enhancing Oxidative Stress and Secretion of Proatherogenic Factors in Advanced Atherosclerosis
by Manoj Kumar Tembhre, Mukesh Kumar Sriwastva, Milind Padmakar Hote, Shikha Srivastava, Priyanka Solanki, Shafaque Imran, Ramakrishnan Lakshmy, Alpana Sharma, Kailash Jaiswal and Ashish Datt Upadhyay
Antioxidants 2022, 11(12), 2343; https://doi.org/10.3390/antiox11122343 - 26 Nov 2022
Cited by 8 | Viewed by 2159
Abstract
Interleukin-33 (IL-33) acts as an ‘alarmin’, and its role has been demonstrated in driving immune regulation and inflammation in many human diseases. However, the precise mechanism of action of IL-33 in regulating neutrophil and macrophage functioning is not defined in advanced atherosclerosis (aAT) [...] Read more.
Interleukin-33 (IL-33) acts as an ‘alarmin’, and its role has been demonstrated in driving immune regulation and inflammation in many human diseases. However, the precise mechanism of action of IL-33 in regulating neutrophil and macrophage functioning is not defined in advanced atherosclerosis (aAT) patients. Further, the role of IL-33 in neutrophil extracellular trap (NET) formation in aAT and its consequent effect on macrophage function is not known. In the present study, we recruited n = 52 aAT patients and n = 52 control subjects. The neutrophils were isolated from both groups via ficoll/percoll-based density gradient centrifugation. The effect of IL-33 on the NET formation ability of the neutrophils was determined in both groups. Monocytes, isolated via a positive selection method, were used to differentiate them into macrophages from each of the study subjects and were challenged by IL-33-primed NETs, followed by the measurement of oxidative stress by calorimetric assay and the expression of the proinflammatory molecules by quantitative PCR (qPCR). Transcript and protein expression was determined by qPCR and immunofluorescence/ELISA, respectively. The increased expression of IL-33R (ST-2) was observed in the neutrophils, along with an increased serum concentration of IL-33 in aAT compared to the controls. IL-33 exacerbates NET formation via specifically upregulating CD16 expression in aAT. IL-33-primed NETs/neutrophils increased the cellular oxidative stress levels in the macrophages, leading to enhanced macrophage necroptosis and the release of atherogenic factors and matrix metalloproteinases (MMPs) in aAT compared to the controls. These findings suggested a pathogenic effect of the IL-33/ST-2 pathway in aAT patients by exacerbating NET formation and macrophage necroptosis, thereby facilitating the release of inflammatory factors and the release of MMPs that may be critical for the destabilization/rupture of atherosclerotic plaques in aAT. Targeting the IL-33/ST-2-NETs axis may be a promising therapeutic target for preventing plaque instability/rupture and its adverse complications in aAT. Full article
(This article belongs to the Special Issue Oxidative Stress and Atherosclerosis)
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26 pages, 4031 KiB  
Article
NADPH Oxidase 5 (NOX5) Overexpression Promotes Endothelial Dysfunction via Cell Apoptosis, Migration, and Metabolic Alterations in Human Brain Microvascular Endothelial Cells (hCMEC/D3)
by Javier Marqués, Joaquín Fernández-Irigoyen, Elena Ainzúa, María Martínez-Azcona, Adriana Cortés, Carmen Roncal, Josune Orbe, Enrique Santamaría and Guillermo Zalba
Antioxidants 2022, 11(11), 2147; https://doi.org/10.3390/antiox11112147 - 29 Oct 2022
Cited by 6 | Viewed by 2209
Abstract
NADPH oxidases (NOX) constitute the main reactive oxygen species (ROS) source in blood vessels. An oxidative stress situation due to ROS overproduction can lead into endothelial dysfunction, a molecular mechanism that precedes cardiovascular diseases (CVDs) such as atherosclerosis, myocardial infarction, and stroke. NOX5 [...] Read more.
NADPH oxidases (NOX) constitute the main reactive oxygen species (ROS) source in blood vessels. An oxidative stress situation due to ROS overproduction can lead into endothelial dysfunction, a molecular mechanism that precedes cardiovascular diseases (CVDs) such as atherosclerosis, myocardial infarction, and stroke. NOX5 is the last discovered member of the NOX family, studied in a lesser extent due to its absence in the rodent genome. Our objective was to describe the phenotypic alterations produced by an oxidative stress situation derived from NOX5 overexpression in an endothelial in vitro model. The in vitro model consists of the hCMEC/D3 cell line, derived from brain microvascular endothelium, infected with a recombinant NOX5-β adenovirus. After an initial proteomic analysis, three phenotypic alterations detected in silico were studied: cell proliferation and apoptosis, general and mitochondrial metabolism, and migration capacity. NOX5 infection of hCMEC/D3 generates a functional protein and an increase in ROS production. This model produced changes in the whole cell proteome. The in silico analysis together with in vitro validations demonstrated that NOX5 overexpression inhibits proliferation and promotes apoptosis, metabolic alterations and cell migration in hCMEC/D3 cells. NOX5 overexpression in endothelial cells leads to phenotypic changes that can lead to endothelial dysfunction, the onset of atherosclerosis, myocardial infarction, and stroke. Full article
(This article belongs to the Special Issue Oxidative Stress and Atherosclerosis)
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Review

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24 pages, 998 KiB  
Review
Antioxidant Properties of Oral Antithrombotic Therapies in Atherosclerotic Disease and Atrial Fibrillation
by Luigi Falco, Viviana Tessitore, Giovanni Ciccarelli, Marco Malvezzi, Antonello D’Andrea, Egidio Imbalzano, Paolo Golino and Vincenzo Russo
Antioxidants 2023, 12(6), 1185; https://doi.org/10.3390/antiox12061185 - 30 May 2023
Cited by 6 | Viewed by 2724
Abstract
The thrombosis-related diseases are one of the leading causes of illness and death in the general population, and despite significant improvements in long-term survival due to remarkable advances in pharmacologic therapy, they continue to pose a tremendous burden on healthcare systems. The oxidative [...] Read more.
The thrombosis-related diseases are one of the leading causes of illness and death in the general population, and despite significant improvements in long-term survival due to remarkable advances in pharmacologic therapy, they continue to pose a tremendous burden on healthcare systems. The oxidative stress plays a role of pivotal importance in thrombosis pathophysiology. The anticoagulant and antiplatelet drugs commonly used in the management of thrombosis-related diseases show several pleiotropic effects, beyond the antithrombotic effects. The present review aims to describe the current evidence about the antioxidant effects of the oral antithrombotic therapies in patients with atherosclerotic disease and atrial fibrillation. Full article
(This article belongs to the Special Issue Oxidative Stress and Atherosclerosis)
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