scholarly journals NADPH Oxidases and Their Role in Atherosclerosis

Biomedicines ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 206 ◽  
Author(s):  
Anastasia V. Poznyak ◽  
Andrey V. Grechko ◽  
Varvara A. Orekhova ◽  
Victoria Khotina ◽  
Ekaterina A. Ivanova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vascular Remodeling ◽  
Current Knowledge ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Current View ◽  
Nadph Oxidases ◽  
Inflammatory Processes ◽  
Atherosclerosis Development ◽  
Initiating Factors

The current view on atherosclerosis positions it as a multifactorial disorder that results from the interplay between lipid metabolism disturbances and inflammatory processes. Oxidative stress is proven to be one of the initiating factors in atherosclerosis development, being implicated both in the inflammatory response and in atherogenic modifications of lipoproteins that facilitate lipid accumulation in the arterial wall. The hallmark of oxidative stress is the elevated level of reactive oxygen species (ROS). Correspondingly, the activity of major ROS-generating enzymes, including nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, xanthine oxidases, and cyclooxygenases, is an important element in atherosclerosis development. In particular, the role of NADPH oxidases in atherosclerosis development has become a subject of intensive research. Aberrant activity of NADPH oxidases was shown to be associated with cardiovascular disease in humans. With regard to atherosclerosis, several important pathological components of the disease development, including endothelial dysfunction, inflammation, and vascular remodeling, involve aberrations in NADPH oxidases functioning. In humans, NADPH oxidases are represented by four isoforms expressed in vascular tissues, where they serve as the main source of ROS during atherogenesis. Moreover, recent studies have demonstrated their impact on vascular remodeling processes. Interestingly, one of the NADPH oxidase isoforms, NOX4, was shown to have an atheroprotective effect. Despite the growing evidence of the crucial involvement of NADPH oxidases in atherosclerosis pathogenesis, the available data still remains controversial. In this narrative review, we summarize the current knowledge of the role of NADPH oxidases in atherosclerosis and outline the future directions of research.

scholarly journals The Role of Oxidative Stress in NAFLD–NASH–HCC Transition—Focus on NADPH Oxidases

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 687
Author(s):  
Daniela Gabbia ◽  
Luana Cannella ◽  
Sara De De Martin
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Current Knowledge ◽  
Mechanisms Of Action ◽  
Nadph Oxidases ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

A peculiar role for oxidative stress in non-alcoholic fatty liver disease (NAFLD) and its transition to the inflammatory complication non-alcoholic steatohepatitis (NASH), as well as in its threatening evolution to hepatocellular carcinoma (HCC), is supported by numerous experimental and clinical studies. NADPH oxidases (NOXs) are enzymes producing reactive oxygen species (ROS), whose abundance in liver cells is closely related to inflammation and immune responses. Here, we reviewed recent findings regarding this topic, focusing on the role of NOXs in the different stages of fatty liver disease and describing the current knowledge about their mechanisms of action. We conclude that, although there is a consensus that NOX-produced ROS are toxic in non-neoplastic conditions due to their role in the inflammatory vicious cycle sustaining the transition of NAFLD to NASH, their effect is controversial in the neoplastic transition towards HCC. In this regard, there are indications of a differential effect of NOX isoforms, since NOX1 and NOX2 play a detrimental role, whereas increased NOX4 expression appears to be correlated with better HCC prognosis in some studies. Further studies are needed to fully unravel the mechanisms of action of NOXs and their relationships with the signaling pathways modulating steatosis and liver cancer development.

scholarly journals Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
White Adipocyte ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

MiR-22-3p Suppresses Vascular Remodeling and Oxidative Stress by Targeting CHD9 during the Development of Hypertension

2021 ◽  
pp. 1-11
Author(s):  
Hanqing Chen ◽  
Xiru Xu ◽  
Zhengqing Liu ◽  
Yong Wu
Keyword(s):  
Oxidative Stress ◽  
Vascular Remodeling ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Spontaneously Hypertensive ◽  
Aortic Smooth Muscle ◽  
Phenotype Switch ◽  
And Oxidative Stress

Hypertension is considered a risk factor for a series of systematic diseases. Known factors including genetic predisposition, age, and diet habits are strongly associated with the initiation of hypertension. The current study aimed to investigate the role of miR-22-3p in hypertension. In this study, we discovered that the miR-22-3p level was significantly decreased in the thoracic aortic vascular tissues and aortic smooth muscle cells (ASMCs) of spontaneously hypertensive rats. Functionally, the overexpression of miR-22-3p facilitated the switch of ASMCs from the synthetic to contractile phenotype. To investigate the underlying mechanism, we predicted 11 potential target mRNAs for miR-22-3p. After screening, chromodomain helicase DNA-binding 9 (CHD9) was validated to bind with miR-22-3p. Rescue assays showed that the co-overexpression of miR-22-3p and CHD9 reversed the inhibitory effect of miR-22-3p mimics on cell proliferation, migration, and oxidative stress in ASMCs. Finally, miR-22-3p suppressed vascular remodeling and oxidative stress in vivo. Overall, miR-22-3p regulated ASMC phenotype switch by targeting CHD9. This new discovery provides a potential insight into hypertension treatment.

scholarly journals NADPH Oxidase as a Therapeutic Target for Oxalate Induced Injury in Kidneys

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sunil Joshi ◽  
Ammon B. Peck ◽  
Saeed R. Khan
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Tissue Injury ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Renal Tissue ◽  
Oxygen Species ◽  
Gene Expressions

A major role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes is to catalyze the production of superoxides and other reactive oxygen species (ROS). These ROS, in turn, play a key role as messengers in cell signal transduction and cell cycling, but when they are produced in excess they can lead to oxidative stress (OS). Oxidative stress in the kidneys is now considered a major cause of renal injury and inflammation, giving rise to a variety of pathological disorders. In this review, we discuss the putative role of oxalate in producing oxidative stress via the production of reactive oxygen species by isoforms of NADPH oxidases expressed in different cellular locations of the kidneys. Most renal cells produce ROS, and recent data indicate a direct correlation between upregulated gene expressions of NADPH oxidase, ROS, and inflammation. Renal tissue expression of multiple NADPH oxidase isoforms most likely will impact the future use of different antioxidants and NADPH oxidase inhibitors to minimize OS and renal tissue injury in hyperoxaluria-induced kidney stone disease.

scholarly journals Role of Mitochondrial Cytochrome P450 2E1 in Healthy and Diseased Liver

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 288
Author(s):  
Julie Massart ◽  
Karima Begriche ◽  
Jessica H. Hartman ◽  
Bernard Fromenty
Keyword(s):  
Oxidative Stress ◽  
Cytochrome P450 ◽  
Liver Disease ◽  
Fatty Liver ◽  
Current Knowledge ◽  
Physiological Role ◽  
Experimental Investigations ◽  
Rat Liver Mitochondria ◽  
Cytochrome P450 2E1

Cytochrome P450 2E1 (CYP2E1) is pivotal in hepatotoxicity induced by alcohol abuse and different xenobiotics. In this setting, CYP2E1 generates reactive metabolites inducing oxidative stress, mitochondrial dysfunction and cell death. In addition, this enzyme appears to play a role in the progression of obesity-related fatty liver to nonalcoholic steatohepatitis. Indeed, increased CYP2E1 activity in nonalcoholic fatty liver disease (NAFLD) is deemed to induce reactive oxygen species overproduction, which in turn triggers oxidative stress, necroinflammation and fibrosis. In 1997, Avadhani’s group reported for the first time the presence of CYP2E1 in rat liver mitochondria, and subsequent investigations by other groups confirmed that mitochondrial CYP2E1 (mtCYP2E1) could be found in different experimental models. In this review, we first recall the main features of CYP2E1 including its role in the biotransformation of endogenous and exogenous molecules, the regulation of its expression and activity and its involvement in different liver diseases. Then, we present the current knowledge on the physiological role of mtCYP2E1, its contribution to xenobiotic biotransformation as well as the mechanism and regulation of CYP2E1 targeting to mitochondria. Finally, we discuss experimental investigations suggesting that mtCYP2E1 could have a role in alcohol-associated liver disease, xenobiotic-induced hepatotoxicity and NAFLD.

scholarly journals The effect of cigarette smoking on endothelial damage and atherosclerosis development – modeled and analyzed using Petri nets

2017 ◽  
Vol 27 (2) ◽  
pp. 211-228 ◽  
Author(s):  
Kaja Chmielewska ◽  
Dorota Formanowicz ◽  
Piotr Formanowicz
Keyword(s):  
Oxidative Stress ◽  
Petri Nets ◽  
Tobacco Smoke ◽  
Endothelial Damage ◽  
Dual Function ◽  
Contributing Factors ◽  
Atherosclerotic Plaque Formation ◽  
Atherosclerosis Development ◽  
The Impact

Abstract Atherosclerosis as one of the crucial causes of cardiovascular diseases (CVD) is the leading reason of death worldwide. One of the contributing factors to this phenomenon is endothelial dysfunction, which is associated with the impact of various agents and their interactions. Tobacco smoke is one of the well known factors here. For better understanding of its significance a model of its impact on atherosclerotic plaque formation has been proposed. The model contains selected aspects of the influence of tobacco smoke, dual function of nitric oxide (NO) (influence of various mechanisms on NO bioavailability), oxidative stress which promotes low density lipoproteins oxidation, macrophages significance and other mechanisms leading to an aggravation of the endothelial disturbances. The model has been built using Petri nets theory and the analysis has been based on t-invariants. This approach allowed to confirm the important role of inflammation and oxidative stress in atherosclerosis development and moreover it has shown the considerable influence of the cigarette smoke.

scholarly journals Role of Cox-2 in Vascular Inflammation: An Experimental Model of Metabolic Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Nicolás F. Renna ◽  
Emiliano R. Diez ◽  
Carina Lembo ◽  
Roberto M. Miatello
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Drinking Water ◽  
Experimental Model ◽  
Vascular Remodeling ◽  
Vascular Inflammation ◽  
Left Ventricular ◽  
Wky Rats ◽  
Cox 2

The objective of this work was to demonstrate the role of COX-2 enzyme at the vascular in experimental model of metabolic syndrome. SHR male WKY rats were employed; they were distributed in 8 groups (n=8each): control (W); W + L: WKY rats receiving 20 mg/kg of lumiracoxib by intraesophageal administration; SHR; SHR + L: SHR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Rats (FFR): WKY rats receiving 10% (w/v) fructose solution in drinking water during all 12 weeks; FFR + L: FFR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Hypertensive Rats (FFHR): SHR receiving 10% (w/v) fructose solution in drinking water during all 12 weeks; and FFHR + L: FFHR + 20 mg/kg of lumiracoxib by intraesophageal administration. Metabolic variables, blood pressure, morphometric variables, and oxidative stress variables were evaluated; also MMP-2 and MMP-9 (collagenases), VCAM-1, and NF-κB by Westernblot or IFI were evaluated. FFHR presented all variables of metabolic syndrome; there was also an increase in oxidative stress variables; vascular remodeling and left ventricular hypertrophy were evidenced along with a significant increase in the expression of the mentioned proinflammatory molecules and increased activity and expression of collagenase. Lumiracoxib was able to reverse vascular remodeling changes and inflammation, demonstrating the involvement of COX-2 in the pathophysiology of vascular remodeling in this experimental model.

scholarly journals Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2786
Author(s):  
Lázaro de Sousa Fideles ◽  
João Antônio Leal de Miranda ◽  
Conceição da Silva Martins ◽  
Maria Lucianny Lima Barbosa ◽  
Helder Bindá Pimenta ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Mechanisms ◽  
Cell Counts ◽  
Histological Damage ◽  
Inflammatory Processes ◽  
Intestinal Mucositis ◽  
Cox 2 ◽  
And Oxidative Stress ◽  
Immunohistochemical Analyses

Intestinal mucositis, characterized by inflammatory and/or ulcerative processes in the gastrointestinal tract, occurs due to cellular and tissue damage following treatment with 5-fluorouracil (5-FU). Rutin (RUT), a natural flavonoid extracted from Dimorphandra gardneriana, exhibits antioxidant, anti-inflammatory, cytoprotective, and gastroprotective properties. However, the effect of RUT on inflammatory processes in the intestine, especially on mucositis promoted by antineoplastic agents, has not yet been reported. In this study, we investigated the role of RUT on 5-FU-induced experimental intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, RUT-50, RUT-100, RUT-200, Celecoxib (CLX), and CLX + RUT-200 groups. The mice were weighed daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis); malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione (GSH) concentrations; mast and goblet cell counts; and cyclooxygenase-2 (COX-2) activity, as well as to perform immunohistochemical analyses. RUT treatment (200 mg/kg) prevented 5-FU-induced histopathological changes and reduced oxidative stress by decreasing MDA concentrations and increasing GSH concentrations. RUT attenuated the inflammatory response by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. These results suggest that the COX-2 pathway is one of the underlying protective mechanisms of RUT against 5-FU-induced intestinal mucositis.

scholarly journals Atypical Chemokine Receptors in Cardiovascular Disease

2019 ◽  
Vol 119 (04) ◽  
pp. 534-541 ◽  
Author(s):  
Selin Gencer ◽  
Emiel van der Vorst ◽  
Maria Aslani ◽  
Christian Weber ◽  
Yvonne Döring ◽  
...  
Keyword(s):  
G Protein ◽  
Chemokine Receptors ◽  
Cellular Response ◽  
Current Knowledge ◽  
G Protein Coupled Receptors ◽  
Signalling Pathways ◽  
Atherosclerosis Development ◽  
G Protein Coupled ◽  
Precise Role

AbstractInflammation has been well recognized as one of the main drivers of atherosclerosis development and therefore cardiovascular diseases (CVDs). It has been shown that several chemokines, small 8 to 12 kDa cytokines with chemotactic properties, play a crucial role in the pathophysiology of atherosclerosis. Chemokines classically mediate their effects by binding to G-protein-coupled receptors called chemokine receptors. In addition, chemokines can also bind to atypical chemokine receptors (ACKRs). ACKRs fail to induce G-protein-dependent signalling pathways and thus subsequent cellular response, but instead are able to internalize, scavenge or transport chemokines. In this review, we will give an overview of the current knowledge about the involvement of ACKR1–4 in CVDs and especially in atherosclerosis development. In the recent years, several studies have highlighted the importance of ACKRs in CVDs, although there are still several controversies and unexplored aspects that have to be further elucidated. A better understanding of the precise role of these atypical receptors may pave the way towards novel and improved therapeutic strategies.

scholarly journals Paraoxonases Activities and Polymorphisms in Elderly and Old-Age Diseases: An Overview

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 118 ◽  
Author(s):  
Débora Levy ◽  
Cadiele Oliana Reichert ◽  
Sérgio Paulo Bydlowski
Keyword(s):  
Oxidative Stress ◽  
Aging Process ◽  
Tissue Injury ◽  
Density Lipoprotein ◽  
The Elderly ◽  
Chromosome 7 ◽  
Oxygen Species ◽  
Structural Homology ◽  
Inflammatory Processes

Aging is defined as the accumulation of progressive organ dysfunction. There is much evidence linking the involvement of oxidative stress in the pathogenesis of aging. With increasing age, susceptibility to the development of diseases related to lipid peroxidation and tissue injury increases, due to chronic inflammatory processes, and production of reactive oxygen species (ROS) and free radicals. The paraoxonase (PON) gene family is composed of three members (PON1, PON2, PON3) that share considerable structural homology and are located adjacently on chromosome 7 in humans. The most studied member product is PON1, a protein associated with high-density lipoprotein with paraoxonase/esterase activity. Nevertheless, all the three proteins prevent oxidative stress. The major aim of this review is to highlight the importance of the role of PON enzymes in the aging process, and in the development of the main diseases present in the elderly: cardiovascular disease, diabetes mellitus, neurodegenerative diseases, and cancer.

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