scholarly journals Glycosylation with O-linked β-N-acetylglucosamine induces vascular dysfunction via production of superoxide anion/reactive oxygen species

2018 ◽  
Vol 96 (3) ◽  
pp. 232-240
Author(s):  
Leonardo Souza-Silva ◽  
Rheure Alves-Lopes ◽  
Jéssica Silva Miguez ◽  
Vanessa Dela Justina ◽  
Karla Bianca Neves ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Protein Expression ◽  
Vascular Function ◽  
Superoxide Anion ◽  
Vascular System ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Endothelium Dependent Relaxation

Overproduction of superoxide anion (•O2−) and O-linked β-N-acetylglucosamine (O-GlcNAc) modification in the vascular system are contributors to endothelial dysfunction. This study tested the hypothesis that increased levels of O-GlcNAc-modified proteins contribute to •O2− production via activation of NADPH oxidase, resulting in impaired vasodilation. Rat aortic segments and vascular smooth muscle cells (VSMCs) were incubated with vehicle (methanol) or O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc) (100 μM). PUGNAc produced a time-dependent increase in O-GlcNAc levels in VSMC and decreased endothelium-dependent relaxation, which was prevented by apocynin and tiron, suggesting that •O2− contributes to endothelial dysfunction under augmented O-GlcNAc levels. Aortic segments incubated with PUGNAc also exhibited increased levels of reactive oxygen species, assessed by dihydroethidium fluorescence, and augmented •O2− production, determined by lucigenin-enhanced chemiluminescence. Additionally, PUGNAc treatment increased Nox-1 and Nox-4 protein expression in aortas and VSMCs. Translocation of the p47phox subunit from the cytosol to the membrane was greater in aortas incubated with PUGNAc. VSMCs displayed increased p22phox protein expression after PUGNAc incubation, suggesting that NADPH oxidase is activated in conditions where O-GlcNAc protein levels are increased. In conclusion, O-GlcNAc levels reduce endothelium-dependent relaxation by overproduction of •O2− via activation of NADPH oxidase. This may represent an additional mechanism by which augmented O-GlcNAc levels impair vascular function.

Coronary endothelial dysfunction after cardiomyocyte-specific mineralocorticoid receptor overexpression

2011 ◽  
Vol 300 (6) ◽  
pp. H2035-H2043 ◽  
Author(s):  
Julie Favre ◽  
Ji Gao ◽  
An Di Zhang ◽  
Isabelle Remy-Jouet ◽  
Antoine Ouvrard-Pascaud ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Coronary Arteries ◽  
Mineralocorticoid Receptor ◽  
Vascular Dysfunction ◽  
Reactive Oxygen ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Coronary Endothelial Dysfunction

The deleterious effects of aldosterone excess demonstrated in cardiovascular diseases might be linked in part to coronary vascular dysfunction. However, whether such vascular dysfunction is a cause or a consequence of the changes occurring in the cardiomyocytes is unclear. Moreover, the possible link between mineralocorticoid receptor (MR)-mediated effects on the cardiomyocyte and the coronary arteries is unknown. Thus we used a mouse model with conditional, cardiomyocyte-specific overexpression of human MR (hMR) and observed the effects on endothelial function in isolated coronary segments. hMR overexpression decreased the nitric oxide (NO)-mediated relaxing responses to acetylcholine in coronary arteries (but not in peripheral arteries), and this was prevented by a 1-mo treatment either with an MR antagonist, vitamin E/vitamin C, or a NADPH oxidase inhibitor. hMR overexpression did not affect coronary endothelial NO synthase content nor its level of phosphorylation on serine 1177, but increased cardiac levels of reactive oxygen species, cardiac NADPH oxidase (NOX) activity, and expression of the NOX subunit gp91phox, which was limited to endothelial cells. Thus an increase in hMR activation, restricted to cardiomyocytes, is sufficient to induce a severe coronary endothelial dysfunction. We suggest a new paracrine mechanism by which cardiomyocytes trigger a NOX-dependent, reactive oxygen species-mediated coronary endothelial dysfunction.

scholarly journals Reactive oxygen species cause endothelial dysfunction in chronic flow overload

2011 ◽  
Vol 110 (2) ◽  
pp. 520-527 ◽  
Author(s):  
X. Lu ◽  
X. Guo ◽  
C. D. Wassall ◽  
M. D. Kemple ◽  
J. L. Unthank ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Shear Stress ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Group Treatment ◽  
Carotid Arteries ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Enos Uncoupling

Although elevation of shear stress increases production of vascular reactive oxygen species (ROS), the role of ROS in chronic flow overload (CFO) has not been well investigated. We hypothesize that CFO increases ROS production mediated in part by NADPH oxidase, which leads to endothelial dysfunction. In six swine, CFO in carotid arteries was induced by contralateral ligation for 1 wk. In an additional group, six swine received apocynin (NADPH oxidase blocker and anti-oxidant) treatment in conjunction with CFO for 1 wk. The blood flow in carotid arteries increased from 189.2 ± 25.3 ml/min (control) to 369.6 ± 61.9 ml/min (CFO), and the arterial diameter increased by 8.6%. The expressions of endothelial nitric oxide synthase (eNOS), p22/p47phox, and NOX2/NOX4 were upregulated. ROS production increased threefold in response to CFO. The endothelium-dependent vasorelaxation was compromised in the CFO group. Treatment with apocynin significantly reduced ROS production in the vessel wall, preserved endothelial function, and inhibited expressions of p22/p47phox and NOX2/NOX4. Although the process of CFO remodeling to restore the wall shear stress has been thought of as a physiological response, the present data implicate NADPH oxidase-produced ROS and eNOS uncoupling in endothelial dysfunction at 1 wk of CFO.

scholarly journals APOCYNIN, AN INHIBITOR OF THE NADPH OXIDASE COMPLEX

2020 ◽  
Vol 17 (34) ◽  
pp. 478-501
Author(s):  
Camila Nascimento GIONGO ◽  
Vanessa Falchetti LOPES ◽  
Diana Fortkamp GRIGOLETTO ◽  
Eduardo Hösel MIRANDA
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Superoxide Anion ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Reactive Oxygen ◽  
Enzyme Complex ◽  
Oxygen Species ◽  
Phagocytic Cells ◽  
Oxidative Species

Apocynin is a phenolic compound isolated from the plant Picrorhiza kurroa Royle ex Benth. Such a compound has been extensively investigated for its therapeutic potential in diseases involving inflammatory processes or oxidative stress due to its ability to inhibit the NADPH oxidase multienzyme complex. This complex consists of two transmembrane proteins (Nox2 and p22phox) and four cytosolic regulatory proteins (p67phox, p47phox, p40phox, and GTPase-Rac) and their activation occurs after the stimulation of phagocytic cells by the mediation of the enzyme myeloperoxidase (MPO). NADPH oxidase is the only enzyme complex that is intended for the production of superoxide anion that is precursor of highly oxidizing substances classified as reactive oxygen species (ROS). NADPH oxidase is an enzyme complex that produces superoxide anion from molecular oxygen. Ta the same time, the superoxide anion is a precursor to reactive oxygen species (ROS) catalyzed by enzymes.These oxidative species, when in excess, can induce burst, causing irreparable tissue damage. They can act by modifying the redox state of DNA, protein or lipid molecules, playing a central role in the development of chronic pathologies and various health complications. One can cite vascular problems, hyperglycemia, diabetes, hypertension, Alzheimer's disease, and cancer, among others. Apocynin, previously activated by MPO, blocks the enzyme complex and prevents the formation of these oxidative species. Therefore, the central biological function of compound is to modulate the action of NADPH oxidase, promoting a positive effect in the prevention/remediation of inflammatory diseases.

Abstract 500: Reactive Oxygen Species and Insufficiency of Nitric Oxide Mediate Enhanced Microvascular Contractility and Impaired Endothelium Dependent Relaxation in Mice With Renal Failure

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Dan Wang ◽  
Cheng Wang ◽  
Christopher S Wilcox
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Endothelial Dysfunction ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Sham Operation ◽  
Oxygen Species ◽  
Channel Dependent ◽  
Microscopy Data ◽  
Endothelium Dependent Relaxation

Background: Cardiovascular disease (CVD) is common and major cause of death and disability in chronic kidney disease (CKD). Since CVD starts with endothelial dysfunction, we tested the hypothesis that reactive oxygen species (ROS) and insufficient nitric oxide (NO) contributed to microvascular contractility and endothelial dysfunction in C57BL/6 mice with normotensive reduced renal mass (RRM) 5/6 nephrectomy, a model of progressive CKD. Methods and Results: Mesenteric arterioles (MAs) were isolated from mice 3 months after sham-operation (Sham) or RRM (n=6/group) and were mounted on Mulvany-Halperin wire myograph, preconstricted with norepinephrine and relaxed with acetylcholine (ACh) for: endothelium-dependent relaxation (EDR); endothelium-dependent relaxation factor (EDRF; NOS-dependent relaxation); endothelium-dependent hyperpolarizing factor (EDHF; K + -channel dependent relaxation) and endothelium-independent relaxation (EIR; sodium nitroprusside). Contractions were tested to endothelium-dependent contracting factor (EDCF; ACh-induced contraction with blocked relaxation pathways); phenylephrine (PE); U-46,619 (thromboxane-prostanoid receptor agonist) and endothelin-1 (ET-1). NO activity (DAF-FM fluorescence) and ROS generation (tempo-9-AC fluorescence) were measured by fluorescence microscopy. Data are mean ±SEM. The MAs from RRM mice had diminished EDR (54 ±5 vs. 77±3%; P<0.01) and EDRF (13±5 vs. 27±4%; P<0.01) with reduced NO activity (0.18 ± 0.05 vs. 0.36± 0.04 ΔUnits; P<0.05), but unchanged EDHF (30±4 vs. 38±4%; NS). These vessels from RRM mice developed an EDCF (14±1 vs. 8±1%; P<0.05) and ACh-induced increased in ROS (0.17±0.03 vs. 0.06±0.02 ΔUnits; P<0.05). Contractile responses were enhanced to U-46,619 (107±4 vs. 87±6, P<0.05) and ET-1 (108±7 vs. 89±4, P<0.05), but not to PE (87±6 vs. 77±8%, NS). Conclusion: mice with RRM developed defective microvascular EDR, EDRF with reduced NO activity and enhanced new ACh-induced EDCF, contractilities to thromboxane and endothelin with increased ROS generation. These microvascular disturbances may contribute to the later development of thrombosis, vascular remodeling and dysfunction in patients with CKD. *D. Wang and C.Wang: Equal contribution

scholarly journals Association of testosterone with estrogen abolishes the beneficial effects of estrogen treatment by increasing ROS generation in aorta endothelial cells

2015 ◽  
Vol 308 (7) ◽  
pp. H723-H732 ◽  
Author(s):  
Tiago J. Costa ◽  
Graziela S. Ceravolo ◽  
Rosangela A. dos Santos ◽  
Maria Aparecida de Oliveira ◽  
Priscila X. Araújo ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Spontaneously Hypertensive Rats ◽  
Reactive Oxygen Species Generation ◽  
Oxygen Species ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Endothelium Dependent Relaxation

Testosterone has been added to hormone replacement therapy to treat sexual dysfunction in postmenopausal women. Whereas estrogen has been associated with vascular protection, the vascular effects of testosterone are contradictory and the effects of its association with estrogen are largely unknown. In this study we determined the effects of testosterone associated with conjugated equine estrogen (CEE) on vascular function using a model of hypertensive postmenopausal female: ovariectomized spontaneously hypertensive rats. Female spontaneously hypertensive rats were divided into sham-operated, ovariectomized (OVX), and OVX treated for 15 days with either CEE alone (OVX+CEE) or associated with testosterone (OVX+CEE+T). Angiotensin II (ANG II)-induced contraction was markedly increased in aortic rings from OVX compared with sham-operated rats. CEE treatment restored ANG-II responses, a beneficial effect abrogated with CEE+T. CEE treatment also increased endothelium-dependent relaxation, which was impaired in OVX rats. This effect was lost by CEE+T. Treatment of aortas with losartan (ANG-II type-1 receptor antagonist) or apocynin (NADPH-oxidase inhibitor) restored the endothelium-dependent relaxation in OVX and CEE+T, establishing an interplay between ANG-II and endothelial dysfunction in OVX and CEE+T. The benefits by CEE were associated with downregulation of NADPH-oxidase subunits mRNA expression and decreased reactive oxygen species generation. The association of testosterone with CEE impairs the benefits of estrogen on OVX-associated endothelial dysfunction and reactive oxygen species generation in rat aorta by a mechanism that involves phosphorylation of the cytosolic NADPH-oxidase subunit p47 phox.

Angiotensin II Mediates High Glucose-Induced TGF-β1 and Fibronectin Upregulation in HPMC through Reactive Oxygen Species

2005 ◽  
Vol 25 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Hyunjin Noh ◽  
Hunjoo Ha ◽  
Mi Ra Yu ◽  
Young Ok Kim ◽  
Ji Hye Kim ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Protein Expression ◽  
High Glucose ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Ang Ii ◽  
Fibronectin Expression ◽  
Tgf Β1

Objective To demonstrate the presence of an independent renin–angiotensin system (RAS) in the peritoneum and to determine the role of locally produced angiotensin (Ang) II in high glucose-induced upregulation of transforming growth factor (TGF)-β1 and fibronectin by human peritoneal mesothelial cells (HPMC). Methods In cultured HPMC, the expression of mRNAs for angiotensinogen, angiotensin-converting enzyme (ACE), Ang II type 1 receptor (AT1), and TGF-β1 was evaluated by real-time polymerase chain reaction; ACE, AT1, and fibronectin proteins by Western blot analysis; and Ang I, Ang II, and TGF-β1 proteins by ELISA. Dichlorofluorescein (DCF)-sensitive cellular reactive oxygen species (ROS) were measured by fluorometry. Results HPMC constitutively expressed all the components of RAS, and 50 mmol/L D-glucose (high glucose) significantly increased angiotensinogen, ACE, and AT1 mRNAs and ACE, AT1, and Ang II proteins. Ang II increased TGF-β1 and fibronectin protein expression and DCF-sensitive cellular ROS. Losartan prevented Ang II-induced increase in cellular ROS. Both losartan and captopril inhibited high glucose-induced upregulation of TGF-β1 and fibronectin expression in HPMC in a dose-dependent manner. Antioxidant catalase and NADPH oxidase inhibitor diphenyleneiodinium effectively inhibited Ang II-induced TGF-β1 and fibronectin protein expression. Conclusions The present data demonstrate that HPMC constitutively express RAS, that Ang II produced by HPMC mediates high glucose-induced upregulation of TGF-β1 and fibronectin expression, and that Ang II-induced TGF-β1 and fibronectin expression in HPMC is mediated by NADPH oxidase-dependent ROS. These data suggest that locally produced Ang II and ROS in the peritoneum may be potential therapeutic targets in peritoneal fibrosis during long-term peritoneal dialysis.

scholarly journals Reactive Oxygen Species from NADPH Oxidase and Mitochondria Participate in the Proliferation of Aortic Smooth Muscle Cells from a Model of Metabolic Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Ocarol López-Acosta ◽  
María de los Angeles Fortis-Barrera ◽  
Miguel Angel Barrios-Maya ◽  
Angélica Ruiz Ramírez ◽  
Francisco Javier Alarcón Aguilar ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Metabolic Syndrome ◽  
Smooth Muscle ◽  
Cell Growth ◽  
Nadph Oxidase ◽  
Superoxide Anion ◽  
Metabolic Diseases ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
And Control

In metabolic diseases, the increased reactive oxygen species (ROS) represents one of the pathogenic mechanisms for vascular disease probably by promoting vascular smooth muscle cell (SMC) proliferation that contributes to the development of arterial remodeling and stenosis, hypertension, and atherosclerosis. Therefore, this work was undertaken to evaluate the participation of ROS from NADPH oxidase and mitochondria in the proliferation of SMCs from the aorta in a model of metabolic syndrome induced by sucrose feeding in rats. After 24 weeks, sucrose-fed (SF) rats develop hypertension, intra-abdominal obesity, hyperinsulinemia, and hyperleptinemia. In addition SMCs from SF rats had a higher growth rate and produce more ROS than control cells. The treatment of SMCs with DPI and apocynin to inhibit NADPH oxidase and with tempol to scavenge superoxide anion significantly blocked the proliferation of both SF and control cells suggesting the participation of NADPH oxidase as a source of superoxide anion. MitoTEMPO, which targets mitochondria within the cell, also significantly inhibited the proliferation of SMCs having a greater effect on cells from SF than from the control aorta. The higher rate of cell growth from the SF aorta is supported by the increased content of cyclophilin A and CD147, proteins involved in the mechanism of cell proliferation. In addition, caldesmon, α-actin, and phosphorylated myosin light chain, contractile phenotype proteins, were found significantly lower in SF cells in no confluent state and increased in confluent state but without difference between both cell types. Our results suggest that ROS from NADPH oxidase and mitochondria significantly participate in the difference found in the rate of cell growth between SF and control cells.

Sign in / Sign up

Export Citation Format

Share Document