A Comprehensive Review of Oxidative Stress as the Underlying Mechanism in Atherosclerosis and the Inefficiency of Antioxidants to Revert this Process

2019 ◽  
Vol 24 (40) ◽  
pp. 4705-4710 ◽  
Author(s):  
Kevin G. Cabezas ◽  
Carmen R. Gómez-Fernandez ◽  
Roberto Vazquez-Padron
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cardiovascular Diseases ◽  
Reactive Oxygen ◽  
Underlying Mechanism ◽  
Plaque Formation ◽  
Oxygen Species ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase

Background: Cardiovascular diseases account for the highest mortality rate in the United States. The major underlying mechanism driving the onset and maintenance of cardiovascular diseases is atherosclerosis. Atherosclerosis is a chronic disease affecting large and medium-size arteries; it proceeds through four main stages along different decades of life, beginning at birth. Atherosclerosis is a consequence of oxidative stress, where homeostasis between endogenous antioxidants and reactive oxygen species is disrupted. Failure of intrinsic antioxidants and prophylactic antioxidant supplements to prevent atherosclerosis formation is an ongoing area of research in the race to avert, manage and cure atherosclerosis. Methods: The purpose of this work was to elucidate the actions of reactive oxygen species and oxidative stress on the formation of atherosclerosis as well as the different stages of atherosclerosis and the different mechanisms to prevent it. Through an extensive review of scientific literature, this paper correlates cell damage caused by oxidative stress to atheromatous plaque formation, as well as an in-depth analysis of high-density lipoproteins and enzymatic and non-enzymatic antioxidant role on atherosclerosis prevention. The antioxidant mechanism is overwhelmed by atherosclerotic processes and fails to be the ideal treatment of atherosclerosis. There is no scientific data that correlates prophylactic and non-prophylactic antioxidant treatment to a decrease in mortality or comorbidities pertaining to atherosclerosis. This is thought to be due to lack of consensus of optimal therapeutic doses, lack of reliable markers indicating which patient is to benefit from therapy and the chemical complexity of antioxidants in vivo. Current treatments for atherosclerosis include HMG-CoA reductase inhibitors which directly target low-density lipoproteins to tackle atherosclerotic plaque formation. Conclusion: HMG-CoA reductase inhibitors are not enough for the treatment of atherosclerosis given the complexity of the disease which has immune, musculoskeletal, genetic and hematologic aspects besides the involvement of lipids and lipoproteins. Therefore, other pharmacologic targets such as the PCSK9 enzyme and NFK- β should be researched in depth as possible treatments for atherosclerosis.

scholarly journals The Role of Nrf2 and PPARγ in the Improvement of Oxidative Stress in Hypertension and Cardiovascular Diseases

2020 ◽  
pp. S541-S553
Author(s):  
I DOVINOVA ◽  
M KVANDOVA ◽  
P BALIS ◽  
L GRESOVA ◽  
M MAJZUNOVA ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cardiovascular Diseases ◽  
Nuclear Receptor ◽  
Redox Regulation ◽  
Reactive Oxygen ◽  
Peroxisome Proliferator ◽  
Oxygen Species ◽  
Response Element ◽  
Stress Oxidative

Reactive oxygen species are an important element of redox regulation in cells and tissues. During physiological processes, molecules undergo chemical changes caused by reduction and oxidation reactions. Free radicals are involved in interactions with other molecules, leading to oxidative stress. Oxidative stress works two ways depending on the levels of oxidizing agents and products. Excessive action of oxidizing agents damages biomolecules, while a moderate physiological level of oxidative stress (oxidative eustress) is necessary to control life processes through redox signaling required for normal cellular operation. High levels of reactive oxygen species (ROS) mediate pathological changes. Oxidative stress helps to regulate cellular phenotypes in physiological and pathological conditions. Nrf2 (nuclear factor erythroid 2-related factor 2, NFE2L2) transcription factor functions as a target nuclear receptor against oxidative stress and is a key factor in redox regulation in hypertension and cardiovascular disease. Nrf2 mediates transcriptional regulation of a variety of target genes. The Keap1-Nrf2-ARE system regulates many detoxification and antioxidant enzymes in cells after the exposure to reactive oxygen species and electrophiles. Activation of Nrf2/ARE signaling is differentially regulated during acute and chronic stress. Keap1 normally maintains Nrf2 in the cytosol and stimulates its degradation through ubiquitination. During acute oxidative stress, oxidized molecules modify the interaction of Nrf2 and Keap1, when Nrf2 is released from the cytoplasm into the nucleus where it binds to the antioxidant response element (ARE). This triggers the expression of antioxidant and detoxification genes. The consequence of long-term chronic oxidative stress is activation of glycogen synthase kinase 3β (GSK-3β) inhibiting Nrf2 activity and function. PPARγ (peroxisome proliferator-activated receptor gamma) is a nuclear receptor playing an important role in the management of cardiovascular diseases, hypertension and metabolic syndrome. PPARγ targeting of genes with peroxisome proliferator response element (PPRE) has led to the identification of several genes involved in lipid metabolism or oxidative stress. PPARγ stimulation is triggered by endogenous and exogenous ligands – agonists and it is involved in the activation of several cellular signaling pathways involved in oxidative stress response, such as the PI3K/Akt/NOS pathway. Nrf2 and PPARγ are linked together with their several activators and Nrf2/ARE and PPARγ/PPRE pathways can control several types of diseases.

scholarly journals Therapeutic Strategies for Oxidative Stress-Related Cardiovascular Diseases: Removal of Excess Reactive Oxygen Species in Adult Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Hyunyun Kim ◽  
Jisoo Yun ◽  
Sang-Mo Kwon
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Stem Cell ◽  
Cardiovascular Diseases ◽  
Progenitor Cells ◽  
Adult Stem Cells ◽  
Reactive Oxygen ◽  
Therapeutic Strategies ◽  
Oxygen Species

Accumulating evidence indicates that acute and chronic uncontrolled overproduction of oxidative stress-related factors including reactive oxygen species (ROS) causes cardiovascular diseases (CVDs), atherosclerosis, and diabetes. Moreover ROS mediate various signaling pathways underlying vascular inflammation in ischemic tissues. With respect to stem cell-based therapy, several studies clearly indicate that modulating antioxidant production at cellular levels enhances stem/progenitor cell functionalities, including proliferation, long-term survival in ischemic tissues, and complete differentiation of transplanted cells into mature vascular cells. Recently emerging therapeutic strategies involving adult stem cells, including endothelial progenitor cells (EPCs), for treating ischemic CVDs have highlighted the need to control intracellular ROS production, because it critically affects the replicative senescence ofex vivoexpanded therapeutic cells. Better understanding of the complexity of cellular ROS in stem cell biology might improve cell survival in ischemic tissues and enhance the regenerative potentials of transplanted stem/progenitor cells. In this review, we will discuss the nature and sources of ROS, drug-based therapeutic strategies for scavenging ROS, and EPC based therapeutic strategies for treating oxidative stress-related CVDs. Furthermore, we will discuss whether primed EPCs pretreated with natural ROS-scavenging compounds are crucial and promising therapeutic strategies for vascular repair.

Are reactive oxygen species important mediators of vascular dysfunction?

2019 ◽  
Vol 15 ◽  
Author(s):  
Gabriel T. do Vale ◽  
Carlos R. Tirapelli
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cardiovascular Diseases ◽  
Vascular Dysfunction ◽  
Critical Role ◽  
Reactive Oxygen ◽  
Oxygen Metabolism ◽  
Ros Generation ◽  
Oxygen Species ◽  
Promising Alternative

Reactive oxygen species (ROS) are reactive derivatives of oxygen metabolism. The ROS generation can be mediated by distinctive enzymatic systems including NADPH oxidases. The components of this enzyme are expressed in endothelial and vascular smooth muscle cells, adventitial fibroblasts, and infiltrating monocytes/macrophages. Oxidative stress is a molecular dysregulation in ROS generation/elimination, which plays a key role in the development of vascular dysfunction in distinctive conditions including hypertension. It is characterized by vascular inflammation, a loss of NO bioavailability and endothelial dysfunction. Considering that oxidative stress is a key mediator of vascular dysfunction, antioxidant therapy with classic antioxidants seemed to be a promising alternative for the treatment of vascular diseases. In this sense, some commonly used drugs for the treatment of cardiovascular diseases such as angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor AT1 antagonists showed antioxidant effects that might have contributed, at least in part, to the beneficial effects of these drugs on the treatment of cardiovascular diseases. The effectiveness of these drugs shows that ROS are in fact important mediators of vascular dysfunction and that angiotensin II plays a critical role in such response.

scholarly journals Reactive oxygen species : A key hallmark of cardiovascullar disease

2019 ◽  
Vol 25 (2) ◽  
Author(s):  
Manorma Singh
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Free Radicals ◽  
Tissue Injury ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Underlying Mechanism ◽  
Cardiovascular Complications ◽  
The Body ◽  
Oxygen Species

Free radicals and oxidants play a dual role as both toxic and beneficial compounds, since they can be either harmful or helpful to the body. They are produced either from normal cell metabolisms in situ or from external sources (pollution, cigarette smoke, radiation, medication). When an overload of free radicals cannot gradually be destroyed, their accumulation in the body generates a phenomenon called oxidative stress. This process plays a major part in the development of chronic and degenerative illness such as cancer, autoimmune disorders, aging, cataract, rheumatoid arthritis, cardiovascular and neurodegenerative diseases. Cardiovascular diseases (CVDs) have been the prime cause of mortality worldwide for decades. However, the underlying mechanism of their pathogenesis is not fully clear yet. It has been already established that reactive oxygen species (ROS) play a vital role in the progression of CVDs. ROS are chemically unstable reactive free radicals containing oxygen, normally produced by xanthine oxidase, nicotinamide adenine dinucleotide phosphate oxidase, lipoxygenases or mitochondria or due to the uncoupling of nitric oxide synthase in vascular cells. When the equilibrium between production of free radicals and antioxidant capacity of human physiology gets altered due to several pathophysiological conditions, oxidative stress is induced, which in turn leads to tissue injury. The information generated by this review aims to provide updated insights into the understanding of the mechanisms behind cardiovascular complications mediated by ROS.

Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Tissue ◽  
Rapid Development ◽  
Reactive Oxygen ◽  
Clinical Aspects ◽  
No Production ◽  
Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

scholarly journals 4-Hydroxychalcone Induces Cell Death via Oxidative Stress in MYCN-Amplified Human Neuroblastoma Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Amnah M. Alshangiti ◽  
Eszter Tuboly ◽  
Shane V. Hegarty ◽  
Cathal M. McCarthy ◽  
Aideen M. Sullivan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cytotoxic Effect ◽  
Neuroblastoma Cells ◽  
Reactive Oxygen ◽  
Prognostic Indicator ◽  
Oxygen Species ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

Neuroblastoma is an embryonal malignancy that arises from cells of sympathoadrenal lineage during the development of the nervous system. It is the most common pediatric extracranial solid tumor and is responsible for 15% of childhood deaths from cancer. Fifty percent of cases are diagnosed as high-risk metastatic disease with a low overall 5-year survival rate. More than half of patients experience disease recurrence that can be refractory to treatment. Amplification of the MYCN gene is an important prognostic indicator that is associated with rapid disease progression and a poor prognosis, highlighting the need for new therapeutic approaches. In recent years, there has been an increasing focus on identifying anticancer properties of naturally occurring chalcones, which are secondary metabolites with variable phenolic structures. Here, we report that 4-hydroxychalcone is a potent cytotoxin for MYCN-amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non-MYCN-amplified SH-SY5Y neuroblastoma cells and to the non-neuroblastoma human embryonic kidney cell line, HEK293t. Moreover, 4-hydroxychalcone treatment significantly decreased cellular levels of the antioxidant glutathione and increased cellular reactive oxygen species. In addition, 4-hydroxychalcone treatment led to impairments in mitochondrial respiratory function, compared to controls. In support of this, the cytotoxic effect of 4-hydroxychalcone was prevented by co-treatment with either the antioxidant N-acetyl-L-cysteine, a pharmacological inhibitor of oxidative stress-induced cell death (IM-54) or the mitochondrial reactive oxygen species scavenger, Mito-TEMPO. When combined with the anticancer drugs cisplatin or doxorubicin, 4-hydroxychalcone led to greater reductions in cell viability than was induced by either anti-cancer agent alone. In summary, this study identifies a cytotoxic effect of 4-hydroxychalcone in MYCN-amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.

scholarly journals Protective Effects of Gintonin on Reactive Oxygen Species-Induced HT22 Cell Damages: Involvement of LPA1 Receptor-BDNF-AKT Signaling Pathway

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4138
Author(s):  
Yeon-Jin Cho ◽  
Sun-Hye Choi ◽  
Ra-Mi Lee ◽  
Han-Sung Cho ◽  
Hyewhon Rhim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Akt Signaling ◽  
Atp Depletion ◽  
Oxygen Species ◽  
Akt Signaling Pathway ◽  
Neuroprotective Effects ◽  
Lpa1 Receptor

Gintonin is a kind of ginseng-derived glycolipoprotein that acts as an exogenous LPA receptor ligand. Gintonin has in vitro and in vivo neuroprotective effects; however, little is known about the cellular mechanisms underlying the neuroprotection. In the present study, we aimed to clarify how gintonin attenuates iodoacetic acid (IAA)-induced oxidative stress. The mouse hippocampal cell line HT22 was used. Gintonin treatment significantly attenuated IAA-induced reactive oxygen species (ROS) overproduction, ATP depletion, and cell death. However, treatment with Ki16425, an LPA1/3 receptor antagonist, suppressed the neuroprotective effects of gintonin. Gintonin elicited [Ca2⁺]i transients in HT22 cells. Gintonin-mediated [Ca2⁺]i transients through the LPA1 receptor-PLC-IP3 signaling pathway were coupled to increase both the expression and release of BDNF. The released BDNF activated the TrkB receptor. Induction of TrkB phosphorylation was further linked to Akt activation. Phosphorylated Akt reduced IAA-induced oxidative stress and increased cell survival. Our results indicate that gintonin attenuated IAA-induced oxidative stress in neuronal cells by activating the LPA1 receptor-BDNF-TrkB-Akt signaling pathway. One of the gintonin-mediated neuroprotective effects may be achieved via anti-oxidative stress in nervous systems.

scholarly journals How to express the antioxidant properties of substances properly?

2021 ◽  
Author(s):  
Małgorzata Olszowy-Tomczyk
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Literature Review ◽  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
Reactive Oxygen ◽  
The Body ◽  
Universal Method ◽  
Oxygen Species ◽  
Good Tool

AbstractOxidative stress, associated with an imbalance between the oxidants (reactive oxygen species) and the antioxidants in the body, contributes to the development of many diseases. The body’s fight against reactive oxygen species is supported by antioxidants. Nowadays, there are too many analytical methods, but there is no one universal technique for assessing antioxidant properties. Moreover, the applied different ways of expressing the results lead to their incompatibility and unreasonable interpretation. The paper is a literature review concerning the most frequent ways of antioxidant activities expression and for an easy and universal method of the obtained results discussion. This paper is an attempt to point out their disadvantages and advantages. The manuscript can support the searching interpretation of the obtained results which will be a good tool for the development of a number of fields, especially medicine what can help in the future detection and treatment of many serious diseases. Graphic abstract

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