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Oxidative Stress in Cardiovascular Disease 2018

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 July 2018) | Viewed by 54980

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Special Issue Editors

Prof. Dr. Lorenza Speranza

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Guest Editor

Department of Medicine and Science of Aging, University "G. D’Annunzio", 66100 Chieti Pescara, Italy
Interests: oxidative stress; cellular biology; disease; network antioxidant; bioactive vegetable; endogenous antioxidant enzymes; inflammation; nutrition; translation medicine; life sciences
Special Issues, Collections and Topics in MDPI journals

Dr. Sara Franceschelli

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Co-Guest Editor

Medicine and Health Science School, Chieti, Italy
Interests: nutrition; cellular biology; oxidative stress; cardiovascular disease; endogenous antioxidant enzymes; bioactive vegetable; molecules
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Low ROX concentration plays a physiological role in cell response regulation by modulating several signal transduction pathways. Chronic oxidative stress, on the contrary, raises the risk of degenerative process and can lead to pathological conditions. Several lines of evidence indicate that oxidative stress is determined by increased concentration of ROS and RNS and amplify the atherosclerotic process by inducing alterations in genic expression, endothelial dysfunction and the promotion of inflammatory processes. Such dysfunction is characterized by a reduced vasodilatation and procoagulant and proinflammatory activity associated with a reduced bioavailability of nitric oxide and excessive production of endothelin 1 (ET-1). In fact, ROS plays a key role in endothelial dysfunction by determining NO inactivation and producing harmful radicals, such as peroxynitrite, which in turn alters the function of endothelial cell proteins, increasing the proatherogenic effect of LDLs. ROS, particularly superoxide anion and hydrogen peroxide, act as signal molecules in heart cells and as second messengers in the activation of several protein chinase like cSrc, p38, Mapk and Akt which regulate the transcription of genes with important functional roles in vascular physiopathology.

Prof. Dr. Lorenza Speranza
Dr. Sara Franceschelli
Guest Editor

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Keywords

oxidative stress
nitric oxide
reactive oxygen species
cardiovascular disease
endothelium
inflammation
reactive nitrosative species
endogenous antioxidant enzymes

Published Papers (9 papers)

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Research

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12 pages, 3380 KiB

Open AccessArticle

Interplay of Glycemic Index, Glycemic Load, and Dietary Antioxidant Capacity with Insulin Resistance in Subjects with a Cardiometabolic Risk Profile

by Cristina Galarregui, María Ángeles Zulet, Irene Cantero, Bertha Araceli Marín-Alejandre, José Ignacio Monreal, Mariana Elorz, Alberto Benito-Boillos, José Ignacio Herrero, Josep Antoni Tur, Itziar Abete and José Alfredo Martínez

Int. J. Mol. Sci. 2018, 19(11), 3662; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19113662 - 20 Nov 2018

Cited by 30 | Viewed by 4521

Abstract

Background: Dietary total antioxidant capacity (TAC), glycemic index (GI), and glycemic load (GL) are accepted indicators of diet quality, which have an effect on diet–disease relationships. The aim of this study was to evaluate potential associations of dietary TAC, GI, and GL with variables related to nutritive status and insulin resistance (IR) risk in cardiometabolic subjects. Methods: A total of 112 overweight or obese adults (age: 50.8 ± 9 years old) were included in the trial. Dietary intake was assessed by a validated 137-item food frequency questionnaire (FFQ), which was also used to calculate the dietary TAC, GI, and GL. Anthropometrics, blood pressure, body composition by dual-energy X-ray absorptiometry (DXA), glycemic and lipid profiles, C-reactive protein (CRP), as well as fatty liver quantification by magnetic resonance imaging (MRI) were assessed. Results: Subjects with higher values of TAC had significantly lower circulating insulin concentration and homeostatic model assessment of insulin resistance (HOMA-IR). Participants with higher values of HOMA-IR showed significantly higher GI and GL. Correlation analyses showed relevant inverse associations of GI and GL with TAC. A regression model evidenced a relationship of HOMA-IR with TAC, GI, and GL. Conclusion: This data reinforces the concept that dietary TAC, GI, and GL are potential markers of diet quality, which have an impact on the susceptible population with a cardiometabolic risk profile. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2018)

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13 pages, 2017 KiB

Open AccessArticle

Immunomodulatory Effects of the Nutraceutical Garlic Derivative Allicin in the Progression of Diabetic Nephropathy

by Abraham Said Arellano Buendía, Montserrat Tostado González, Omegar Sánchez Reyes, Fernando Enrique García Arroyo, Raúl Argüello García, Edilia Tapia, Laura Gabriela Sánchez Lozada and Horacio Osorio Alonso

Int. J. Mol. Sci. 2018, 19(10), 3107; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19103107 - 11 Oct 2018

Cited by 37 | Viewed by 4743

Abstract

Diabetic nephropathy (DN) is presently the primary cause of chronic kidney disease and end-stage renal disease (ESRD). It has been suggested that inflammation and oxidative stress, in addition to or in concert with the metabolic changes, plays an important role in the maintenance and progression of the disease. Therefore, attenuating or blocking these mechanisms may be a therapeutic target to delay the progression of the disease. Diallyl thiosulfinate (allicin), a compound derived from garlic, inhibits free radical formation, increases glutathione synthesis and decreases the levels of proinflammatory molecules in vitro. This research aimed to assess the effect of allicin on oxidative stress and inflammation-induced diabetes. Animals were divided into control and diabetes (streptozotocin 50 mg/kg i.p.), and maintained for 30 days. After 30 days, the group of diabetic animals was subdivided into diabetes and allicin-treated diabetes (16 mg/kg/day oral gavage). The three experimental groups were maintained for another month. We analyzed the status of renal function, oxidative stress and proinflammatory cytokines. The untreated diabetic group showed hyperglycemia and increased diuresis, creatinine clearance, proteinuria, glycosuria and urinary excretion of N-acetyl-β-d-glucosaminidase (NAG), as well as increased oxidative stress and the expression of interleukin 1β (IL-1β), IL-6, nuclear factor kappa beta (NFκβ) and transforming growth factor-β1 (TGF-β1) in plasma and kidney. In contrast, the inhibitor of NFκβ (Iκβ) is decreased in the cortex. It has been demonstrated that the allicin treatment decreases hyperglycemia, polyuria, and NAG excretion. The oxidative stress and proinflammatory cytokines were also reduced by the allicin treatment. In conclusion, allicin delays the progression of diabetic nephropathy through antioxidant and anti-inflammatory mechanisms. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2018)

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19 pages, 4326 KiB

Open AccessArticle

Combination ART-Induced Oxidative/Nitrosative Stress, Neurogenic Inflammation and Cardiac Dysfunction in HIV-1 Transgenic (Tg) Rats: Protection by Mg

by I. Tong Mak, Joanna J. Chmielinska, Christopher F. Spurney, William B. Weglicki and Jay H. Kramer

Int. J. Mol. Sci. 2018, 19(8), 2409; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19082409 - 15 Aug 2018

Cited by 9 | Viewed by 4252

Abstract

Chronic effects of a combination antiretroviral therapy (cART = tenofovir/emtricitatine + atazanavir/ritonavir) on systemic and cardiac oxidative stress/injury in HIV-1 transgenic (Tg) rats and protection by Mg-supplementation were assessed. cART (low doses) elicited no significant effects in normal rats, but induced time-dependent oxidative/nitrosative stresses: 2.64-fold increased plasma 8-isoprostane, 2.0-fold higher RBC oxidized glutathione (GSSG), 3.2-fold increased plasma 3-nitrotyrosine (NT), and 3-fold elevated basal neutrophil superoxide activity in Tg rats. Increased NT staining occurred within cART-treated HIV-Tg hearts, and significant decreases in cardiac systolic and diastolic contractile function occurred at 12 and 18 weeks. HIV-1 expression alone caused modest levels of oxidative stress and cardiac dysfunction. Significantly, cART caused up to 24% decreases in circulating Mg in HIV-1-Tg rats, associated with elevated renal NT staining, increased creatinine and urea levels, and elevated plasma substance P levels. Strikingly, Mg-supplementation (6-fold) suppressed all oxidative/nitrosative stress indices in the blood, heart and kidney and substantially attenuated contractile dysfunction (>75%) of cART-treated Tg rats. In conclusion, cART caused significant renal and cardiac oxidative/nitrosative stress/injury in Tg-rats, leading to renal Mg wasting and hypomagnesemia, triggering substance P-dependent neurogenic inflammation and cardiac dysfunction. These events were effectively attenuated by Mg-supplementation likely due to its substance P-suppressing and Mg’s intrinsic anti-peroxidative/anti-calcium properties. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2018)

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13 pages, 3523 KiB

Open AccessArticle

The Effects of Long-Term, Low- and High-Dose Beta-Carotene Treatment in Zucker Diabetic Fatty Rats: The Role of HO-1

by Evelin Csepanyi, Attila Czompa, Peter Szabados-Furjesi, Istvan Lekli, Jozsef Balla, Gyorgy Balla, Arpad Tosaki and Istvan Bak

Int. J. Mol. Sci. 2018, 19(4), 1132; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19041132 - 10 Apr 2018

Cited by 12 | Viewed by 4220

Abstract

Nowadays, there is a growing interest in compounds derived from plants as potential raw materials for drug development. One of the most studied compounds is beta-carotene (BC). Several clinical studies can be found investigating the cardiovascular effects of BC, however, all these results are controversial. There is an increasing body of evidence showing that besides the well-known antioxidant properties, under strong oxidative circumstances, BC could become prooxidant as well. In this study, we investigated the effects of long-term, low- and high-dose BC treatment in ischemic/reperfused (ISA/REP) hearts isolated from Zucker diabetic fatty (ZDF) rats. The animals were treated with various daily doses of BC for 4 weeks and then hearts were isolated and subjected to 30 min of global ischemia (ISA) followed by 120 min of reperfusion (REP). Blood glucose levels were measured before, after two weeks, and at the end of the treatment. In isolated hearts, the myocardial function was registered. At the end of the reperfusion period, the infarct size (IS) and heme oxygenase-1 (HO-1) expression were measured. The results showed that a low dose of BC treatment significantly improved postischemic recovery, which was reflected in a decreased IS. Interestingly, when BC was applied at high concentrations, the observed protective effects were lost. Although BC treatment increased HO-1 expression, we did not observe a better heart function and/or decreased IS in the high-dose-treated group. Glucose tolerance tests showed a concentration-independent decrease in blood glucose levels. Our results suggest that long-term, low-dose BC treatment could be effective in the treatment of type-2-diabetes and related cardiovascular diseases. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2018)

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13 pages, 5918 KiB

Open AccessArticle

Baicalein Rescues Delayed Cooling via Preservation of Akt Activation and Akt-Mediated Phospholamban Phosphorylation

by Zuohui Shao, Sy-Jou Chen, Xiangdong Zhu, Chunpei Lee, Hsien-Hao Huang, Angelo Meliton, Changqing Li, Terry L. Vanden Hoek and Jing Li

Int. J. Mol. Sci. 2018, 19(4), 973; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19040973 - 24 Mar 2018

Cited by 4 | Viewed by 3378

Abstract

Cooling reduces the ischemia/reperfusion (I/R) injury seen in sudden cardiac arrest (SCA) by decreasing the burst of reactive oxygen species (ROS). Its cardioprotection is diminished when delay in reaching the target temperature occurs. Baicalein, a flavonoid derived from the root of Scutellaria baicalensis Georgi, possesses antioxidant properties. Therefore, we hypothesized that baicalein can rescue cooling cardioprotection when cooling is delayed. Two murine cardiomyocyte models, an I/R model (90 min ischemia/3 h reperfusion) and stunning model (30 min ischemia/90 min reperfusion), were used to assess cell survival and contractility, respectively. Cooling (32 °C) was initiated either during ischemia or during reperfusion. Cell viability and ROS generation were measured. Cell contractility was evaluated by real-time phase-contrast imaging. Our results showed that cooling reduced cell death and ROS generation, and this effect was diminished when cooling was delayed. Baicalein (25 µM), given either at the start of reperfusion or start of cooling, resulted in a comparable reduction of cell death and ROS production. Baicalein improved phospholamban phosphorylation, contractility recovery, and cell survival. These effects were Akt-dependent. In addition, no synergistic effect was observed with the combined treatments of cooling and baicalein. Our data suggest that baicalein may serve as a novel adjunct therapeutic strategy for SCA resuscitation. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2018)

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15 pages, 1226 KiB

Open AccessArticle

High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice

by Gina Sánchez, Felipe Araneda, Juan Pedro Peña, José Pablo Finkelstein, Jaime A. Riquelme, Luis Montecinos, Genaro Barrientos, Paola Llanos, Zully Pedrozo, Matilde Said, Ricardo Bull and Paulina Donoso

Int. J. Mol. Sci. 2018, 19(2), 533; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19020533 - 10 Feb 2018

Cited by 26 | Viewed by 5224

Abstract

Ventricular arrhythmias are a common cause of sudden cardiac death, and their occurrence is higher in obese subjects. Abnormal gating of ryanodine receptors (RyR2), the calcium release channels of the sarcoplasmic reticulum, can produce ventricular arrhythmias. Since obesity promotes oxidative stress and RyR2 are redox-sensitive channels, we investigated whether the RyR2 activity was altered in obese mice. Mice fed a high fat diet (HFD) became obese after eight weeks and exhibited a significant increase in the occurrence of ventricular arrhythmias. Single RyR2 channels isolated from the hearts of obese mice were more active in planar bilayers than those isolated from the hearts of the control mice. At the molecular level, RyR2 channels from HFD-fed mice had substantially fewer free thiol residues, suggesting that redox modifications were responsible for the higher activity. Apocynin, provided in the drinking water, completely prevented the appearance of ventricular arrhythmias in HFD-fed mice, and normalized the activity and content of the free thiol residues of the protein. HFD increased the expression of NOX4, an isoform of NADPH oxidase, in the heart. Our results suggest that HFD increases the activity of RyR2 channels via a redox-dependent mechanism, favoring the appearance of ventricular arrhythmias. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2018)

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1122 KiB

Open AccessArticle

Elevation of Serum APE1/Ref-1 in Experimental Murine Myocarditis

by Seon-Ah Jin, Byung-Kwan Lim, Hee Jung Seo, Sun Kyeong Kim, Kye Taek Ahn, Byeong Hwa Jeon and Jin-Ok Jeong

Int. J. Mol. Sci. 2017, 18(12), 2664; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18122664 - 08 Dec 2017

Cited by 15 | Viewed by 4006

Abstract

Myocarditis is an inflammatory disease of the myocardium that causes cardiogenic shock and death. However, endomyocardial biopsy that is, the gold standard for a diagnosis is limited. Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a multifunctional protein, which is involved in DNA-based excision repair pathway, and in redox signaling, its changes are observed in various cardiovascular diseases including hypertension and coronary artery disease. We analyzed serum APE1/Ref-1 in experimental murine myocarditis. To induce myocarditis, coxsackievirus B3 was injected intraperitoneally to BALB/c mice. The serum APE1/Ref-1, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin I were measured. The histology and virus titers measurements were performed. The troponin I and inflammation were significantly elevated at day 3, peaked to day 7 and decreased at day 10. The NT-proBNP and virus titers were significantly peaked at day 3, and dropped at day 7 and 10. The serum APE1/Ref-1 was gradually raised and its elevation is still maintained until a later time, namely day 10. Also, its level was positively correlated with myocardial inflammation, reflecting severity of myocardial injury. We suggest that serum APE1/Ref-1 can be used to assess for myocardial injury in viral myocarditis without endomyocardial biopsy. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2018)

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Review

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1300 KiB

Open AccessReview

Oxidative Stress in Cardiovascular Diseases: Involvement of Nrf2 Antioxidant Redox Signaling in Macrophage Foam Cells Formation

by Bee Kee Ooi, Bey Hing Goh and Wei Hsum Yap

Int. J. Mol. Sci. 2017, 18(11), 2336; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18112336 - 05 Nov 2017

Cited by 96 | Viewed by 12042

Abstract

Oxidative stress is an important risk factor contributing to the pathogenesis of cardiovascular diseases. Oxidative stress that results from excessive reactive oxygen species (ROS) production accounts for impaired endothelial function, a process which promotes atherosclerotic lesion or fatty streaks formation (foam cells). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor involved in cellular redox homeostasis. Upon exposure to oxidative stress, Nrf2 is dissociated from its inhibitor Keap-1 and translocated into the nucleus, where it results in the transcriptional activation of cell defense genes. Nrf2 has been demonstrated to be involved in the protection against foam cells formation by regulating the expression of antioxidant proteins (HO-1, Prxs, and GPx1), ATP-binding cassette (ABC) efflux transporters (ABCA1 and ABCG1) and scavenger receptors (scavenger receptor class B (CD36), scavenger receptor class A (SR-A) and lectin-type oxidized LDL receptor (LOX-1)). However, Nrf2 has also been reported to exhibit pro-atherogenic effects. A better understanding on the mechanism of Nrf2 in oxidative stress-induced cardiac injury, as well as the regulation of cholesterol uptake and efflux, are required before it can serve as a novel therapeutic target for cardiovascular diseases prevention and treatment. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2018)

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Reductive Stress in Inflammation-Associated Diseases and the Pro-Oxidant Effect of Antioxidant Agents

by Israel Pérez-Torres, Verónica Guarner-Lans and María Esther Rubio-Ruiz

Int. J. Mol. Sci. 2017, 18(10), 2098; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18102098 - 05 Oct 2017

Cited by 144 | Viewed by 11585

Abstract

Abstract: Reductive stress (RS) is the counterpart oxidative stress (OS), and can occur in response to conditions that shift the redox balance of important biological redox couples, such as the NAD⁺/NADH, NADP⁺/NADPH, and GSH/GSSG, to a more reducing state. Overexpression of antioxidant enzymatic systems leads to excess reducing equivalents that can deplete reactive oxidative species, driving the cells to RS. A feedback regulation is established in which chronic RS induces OS, which in turn, stimulates again RS. Excess reducing equivalents may regulate cellular signaling pathways, modify transcriptional activity, induce alterations in the formation of disulfide bonds in proteins, reduce mitochondrial function, decrease cellular metabolism, and thus, contribute to the development of some diseases in which NF-κB, a redox-sensitive transcription factor, participates. Here, we described the diseases in which an inflammatory condition is associated to RS, and where delayed folding, disordered transport, failed oxidation, and aggregation are found. Some of these diseases are aggregation protein cardiomyopathy, hypertrophic cardiomyopathy, muscular dystrophy, pulmonary hypertension, rheumatoid arthritis, Alzheimer’s disease, and metabolic syndrome, among others. Moreover, chronic consumption of antioxidant supplements, such as vitamins and/or flavonoids, may have pro-oxidant effects that may alter the redox cellular equilibrium and contribute to RS, even diminishing life expectancy. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2018)

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