Reactive oxygen species,endothelial damage

Recent clinical cohort study shows that testosterone therapy increases cardiovascular diseases in men with low testosterone levels, excessive circulating androgen levels may play a detrimental role in the vascular system, while the potential mechanism and effect of testosterone exposure on the vascular function in offspring is still unknown. Our preliminary results showed that perinatal testosterone exposure in mice induces estrogen receptor β (ERβ) suppression in endothelial progenitor cells (EPCs) in offspring but not mothers, while estradiol (E2) had no effect...

Metastatic melanoma is an aggressive and deadly disease. Therapeutic advance has been achieved by antitumor chemo- and radiotherapy. These modalities involve the generation of reactive oxygen and nitrogen species, affecting cellular viability, migration, and immunogenicity. Such species are also created by cold physical plasma, an ionized gas capable of redox modulating cells and tissues without thermal damage. Cold plasma has been suggested for anticancer therapy. Here, melanoma cell toxicity, motility, and immunogenicity of murine metastatic melanoma cells were investigated following plasma exposure in vitro...

Irradiation of normal tissues leads to acute increase in reactive oxygen/nitrogen species that serve as intra- and inter-cellular signaling to alter cell and tissue function. In the case of chest irradiation, it can affect the heart, blood vessels, and lungs, with consequent tissue remodelation and adverse side effects and symptoms. This complex process is orchestrated by a large number of interacting molecular signals, including cytokines, chemokines, and growth factors. Inflammation, endothelial cell dysfunction, thrombogenesis, organ dysfunction, and ultimate failing of the heart occur as a pathological entity - "radiation-induced heart disease" (RIHD) that is major source of morbidity and mortality...

BACKGROUND: Several studies associated high-fat intakes with a high incidence of age-related macular degeneration (AMD). Lutein and Zeaxanthin isomers (L/Zi) may counteract reactive oxygen species produced by oxidative stress. The present study was conducted to determine the possible effects of L/Zi administration on lipid profile, protein genes associated with oxidative stress and inflammation pathways in the obesity induced by a high-fat diet (HFD) in rodents. METHODS: Twenty-eight male Wistar rats were allocated into four groups as follows: (i) Control, (ii) Control + L/Zi, (iii) High Fat Diet (HFD), and (iv) HFD+ L/Z...

Heme oxygenase‑1 (HO‑1), as an inducible and cytoprotective enzyme, has a protective effect against cellular oxidative stress. In the present study, cholesterol was used to induce lipid overload and increase reactive oxygen species (ROS), leading to oxidative stress in EA.hy926 cells. In the present study, western blotting and immunofluorescence analysis were used to detect the expression level of important molecules in the metabolism process of cholesterol. It was confirmed that cholesterol stimulation upregulated the expression of HO‑1 in a time‑dependent manner via the activation and translocation of nuclear factor erythroid 2‑related factor 2 (Nrf2), activation of the mitogen‑activated protein kinase (MAPK)/extracellular signal‑regulated kinase (ERK) signaling pathway and increasing intercellular Ca2+ ([Ca2+]i) concentration...

Atherosclerosis is a chronic inflammatory disease formed by the accumulation of lipids in the innermost layer and large-caliber artery (tunica intima). This accumulation, along with platelet factors, stimulates the proliferation of muscle cells in this region. Over than 400 genes may be related to the pathology since they regulate endothelial function, coagulation, inflammation, metabolism of amino acids, lipids, and carbohydrates. Glutathione S-transferases (GST) are enzymes that catalyze the polymorphic detoxification of metabolites produced by oxidative stress within the cells, which is induced by reactive oxygen species...

Recent studies have revealed that particulate matter (PM) exert deleterious effects on vascular function. Pulmonary artery endothelial cells (HPAEC), which are involved in the vasomotricity regulation, can be a direct target of inhaled particles. Modifications in calcium homeostasis and oxidative stress are critical events involved in the physiopathology of vascular diseases. The objectives of this study were to assess the effects of PM2.5 on oxidative stress and calcium signaling in HPAEC. Different endpoints were studied, (i) intrinsic and intracellular production of reactive oxygen species (ROS) by the H2DCF-DA probe, (ii) intrinsic, intracellular and mitochondrial production of superoxide anion (O2(-)) by electronic paramagnetic resonance spectroscopy and MitoSOX probe, (iii) reactive nitrosative species (RNS) production by Griess reaction, and (vi) calcium signaling by the Fluo-4 probe...

The antioxidant activity of genistein is associated with preventing atherosclerosis; however, the underlying mechanisms are not fully understood. In this study, human umbilical vein endothelial cells (HUVECs) were pretreated with genistein at different concentrations (10nM, 100nM and 1000nM) for 6h and then exposed to ox-LDL (50mg/L) for another 24h. Results showed that genistein restrained reactive oxygen species (ROS) and malondialdehyde (MDA) production, and ameliorated the inhibitory effect on superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) activity elicited by ox-LDL stimulation...

Endothelial microparticles (EMPs) are endothelium-derived submicron vesicles that are released in response to diverse stimuli and are elevated in cardiovascular disease, which is correlated with risk factors. This study investigates the effect of EMPs on endothelial cell function and dysfunction in a model of free fatty acid (FFA) palmitate-induced oxidative stress. EMPs were generated from TNF-α-stimulated HUVECs and quantified by using flow cytometry. HUVECs were treated with and without palmitate in the presence or absence of EMPs...

Vascular disease and heart failure impart an enormous burden in terms of global morbidity and mortality. Although there are many different causes of cardiac and vascular disease, most causes share an important pathological mechanism: oxidative stress. In the failing heart, oxidative stress occurs in the myocardium and correlates with left ventricular dysfunction. Reactive oxygen species (ROS) negatively affect myocardial calcium handling, cause arrhythmia, and contribute to cardiac remodeling by inducing hypertrophic signaling, apoptosis, and necrosis...

High levels of glucose (HG) induce reactive oxygen species-mediated oxidative stress in endothelial cells (ECs), which leads to endothelial dysfunction and tissue damage. However, the molecular mechanisms involved in HG-induced endothelial oxidative stress and damage remain elusive. Here we show that cellular ATP level-modulated p53 Thr55 phosphorylation plays a critical role in the process. Upon HG exposure, the elevated ATP levels induced the kinase activity of TAF1 (TBP-associated factor 1), which leads to p53 Thr55 phosphorylation...

BACKGROUND AND PURPOSE: Reperfusion therapy by mechanical thrombectomy is used to treat acute ischemic stroke. However, reactive oxygen species generation after reperfusion therapy causes cerebral ischemia-reperfusion injury, which aggravates cerebral infarction. There is limited evidence for clinical efficacy in stroke for antioxidants. Here, we developed a novel core-shell type nanoparticle containing 4-amino-4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (nitroxide radical-containing nanoparticles [RNPs]) and investigated its ability to scavenge reactive oxygen species and confer neuroprotection...

BACKGROUND: Anesthesiologists administer excess supplemental oxygen (hyper-oxygenation) to patients during surgery to avoid hypoxia. Hyper-oxygenation, however, may increase the generation of reactive oxygen species and cause oxidative damage. In cardiac surgery, increased oxidative damage has been associated with postoperative kidney and brain injury. We hypothesize that maintenance of normoxia during cardiac surgery (physiologic oxygenation) decreases kidney injury and oxidative damage compared to hyper-oxygenation...

Endothelial cells are considered candidates for involvement in the pathogenesis of diabetic vascular complications, and prevention of endothelial cell damage may be important in pharmacological attempts to prevent such complications. In the present study, I explored whether extracts of Chrysanthemum zawadskii (CZE) could prevent oxidative damage and dysfunction of a vascular endothelial cell line caused by the highly reducing sugar, 2-deoxy-D-ribose (dRib), and dysfunction of a vascular endothelial cell line...

There is evidence that angiotensin II (Ang II) may impair the functions of endothelial progenitor cells (EPCs). It was revealed that DJ-1 could resist oxidative stress. In this study, we investigated whether DJ-1 could protect EPCs against Ang II-induced cell damage. The proliferation and migration of EPCs were strongly reduced in the Ang II group and were increased by overexpression of DJ-1. Western blotting indicated that the increased expression of the senescence marker β-galactosidase and decreased expression of adhesion molecules (ICAM-1, VCAM-1) induced by Ang II were reversed after Ad-DJ-1 transfection...

Hemopexin protects against heme toxicity in hemolytic diseases and conditions, sepsis and sickle cell disease. This protection is sustained by heme-hemopexin complexes present in biological fluids that resist oxidative damage during heme-driven inflammation. However, apo-hemopexin is vulnerable to inactivation by reactive nitrogen and oxygen species that covalently modify amino acids. The consequent nitration of amino acids is considered a selective and specific effect reflecting biological events. Using liquid chromatography-tandem mass spectrometry, we discovered low endogenous levels of tyrosine nitration in the peptide YYCFQGNQFLR of human hemopexin, which was similarly nitrated in rabbit and rat hemopexins...

Reactive oxygen species (ROS) are reactive intermediates of molecular oxygen that act as important second messengers within the cells; however, an imbalance between generation of reactive ROS and antioxidant defense systems represents the primary cause of endothelial dysfunction, leading to vascular damage in both metabolic and atherosclerotic diseases. Endothelial activation is the first alteration observed, and is characterized by an abnormal pro-inflammatory and pro-thrombotic phenotype of the endothelial cells lining the lumen of blood vessels...

In this study, we found that exposure to α-pyrrolidinononanophenone (α-PNP), a highly lipophilic synthetic cathinone, provokes apoptosis of human neuronal SK-N-SH cells. The drug sensitivity of the cells (50% lethal concentration of 12μM) was similar to those of aortic endothelial and smooth muscle cells, and was higher than those of cells derived from colon, liver, lung and kidney, suggesting that α-PNP overdose and abuse cause serious damage in central nervous and vascular systems. SK-N-SH cell treatment with lethal concentrations (20 and 50μM) of α-PNP facilitated the reactive oxygen species (ROS) production...

The cornea is the anterior transparent surface and the main refracting structure of the eye. Mitochondrial dysfunction and oxidative stress are implicated in the pathogenesis of inherited (e.g. Kearns Sayre Syndrome) and acquired corneal diseases (e.g. keratoconus and Fuchs endothelial corneal dystrophy). Both antioxidants and reactive oxygen species are found in the healthy cornea. There is increasing evidence of imbalance in the oxidative balance and mitochondrial function in the cornea in disease states...

Placental activation of the renin-angiotensin system (RAS) plays a key role in the pathogenesis of preeclampsia. Reactive oxygen species (ROS) are thought to affect placental angiogenesis, which is critical for preventing preeclampsia pathology. We examined the role of ROS in preeclampsia by genetically modifying the Keap1-Nrf2 pathway, a cellular antioxidant defense system, in a mouse model of RAS-induced preeclampsia. Nrf2 deficiency would be expected to impair cellular antioxidant responses; however, Nrf2 deficiency in preeclamptic mice improved maternal and fetal survival, ameliorated intra-uterine growth retardation, and augmented oxidative DNA damage...