Rapid NOS-1-derived nitric oxide and peroxynitrite formation act as signaling agents for inducible NOS-2 expression in vascular smooth muscle cells

Scheschowitsch, Karin; Moraes, João Alfredo; Barja‐Fidalgo, Christina; Assreuy, Jamil

doi:10.1016/j.phrs.2015.08.001

Cited by 16 publications

(12 citation statements)

References 56 publications

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“…Since NOXs represent enzymes producing primarily ROS and NOX-1 and NOX-2 are present in endothelial cells [27] and in vascular smooth muscle cells [28,29,30], we propose that high levels of human plasma sEng in mice fed a high-fat diet induce oxidative stress in the aortic wall.…”

Section: Discussionmentioning

confidence: 99%

High Levels of Soluble Endoglin Induce a Proinflammatory and Oxidative-Stress Phenotype Associated with Preserved NO-Dependent Vasodilatation in Aortas from Mice Fed a High-Fat Diet

et al. 2016

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Aims: A soluble form of endoglin (sEng) was proposed to participate in the induction of endothelial dysfunction in small blood vessels. Here, we tested the hypothesis that high levels of sEng combined with a high-fat diet induce endothelial dysfunction in an atherosclerosis-prone aorta. Methods and Results: Six-month-old female and male transgenic mice overexpressing human sEng (Sol-Eng⁺) with low (Sol-Eng⁺low) or high (Sol-Eng⁺high) levels of plasma sEng were fed a high-fat rodent diet containing 1.25% cholesterol and 40% fat for 3 months. The plasma cholesterol and mouse sEng levels did not differ in the Sol-Eng⁺high and Sol-Eng⁺low mice. The expression of proinflammatory (P-selectin, ICAM-1, pNFκB and COX-2) and oxidative-stress-related markers (HO-1, NOX-1 and NOX-2) in the aortas of Sol-Eng⁺high female mice was significantly higher than in Sol-Eng⁺low female mice. Endothelium-dependent vasodilatation induced by acetylcholine was preserved better in the Sol-Eng⁺high female mice than in the Sol-Eng⁺low female mice. Conclusion: These results suggest that high concentrations of sEng in plasma in combination with a high-fat diet induce the simultaneous activation of proinflammatory, pro-oxidative and vasoprotective mechanisms in mice aorta and the balance of these biological processes determines whether the final endothelial phenotype is adaptive or maladaptive.

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Section: Discussionmentioning

confidence: 99%

High Levels of Soluble Endoglin Induce a Proinflammatory and Oxidative-Stress Phenotype Associated with Preserved NO-Dependent Vasodilatation in Aortas from Mice Fed a High-Fat Diet

et al. 2016

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“…Moreover, Duma and colleagues showed that nNOS knockout animals or wildtype animals treated with a nNOS inhibitor, when subjected to CLP model, exhibited reduction of the expression of iNOS and lower NO production than CLP control animals (12). Also, nNOS-derived NO is shown to act as signalling agent for iNOS expression in vascular smooth muscle cells (29). .…”

Section: Discussionmentioning

confidence: 99%

Neuronal Nitric Oxide Synthase is Involved in Vascular Hyporeactivity and Multiple Organ Dysfunction Associated with Hemorrhagic Shock

Chiazza

Collino

Assreuy

et al. 2016

Shock

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Severe hemorrhage can lead to global ischemia and hemorrhagic shock (HS), resulting in multiple organ failure (MOF) and death. Restoration of blood flow and re-oxygenation is associated with an exacerbation of tissue injury and inflammatory response. The neuronal nitric oxide synthase (nNOS) has been implicated in vascular collapse and systemic inflammation of septic shock; however, the role of nNOS in HS is poorly understood. The aim of this study was to evaluate the role of nNOS in the MOF associated with HS.Rats were subjected to HS under anesthesia. Mean arterial pressure was reduced to 30 mmHg for 90 min, followed by resuscitation with shed blood. Rats were randomly treated with two chemically distinct nNOS inhibitors [ARL 17477 (1 mg/kg) and 7-nitroindazol (5 mg/kg)] or vehicle upon resuscitation. Four hours later, parameters of organ injury and dysfunction were assessed.HS was associated with MOF development. Inhibition of nNOS activity at resuscitation protected rats against the MOF and vascular dysfunction. In addition, treatment of HS rats with nNOS inhibitors attenuated neutrophil infiltration into target organs and decreased the activation of NF-κB, iNOS expression, NO production, and nitrosylation of proteins. Furthermore, nNOS inhibition also reduced the levels of pro-inflammatory cytokines TNF-α and IL-6 in HS rats.In conclusion, two distinct inhibitors of nNOS activity reduced the MOF, vascular dysfunction, and the systemic inflammation associated with HS. Thus, nNOS inhibitors may be useful as an adjunct therapy before fluids and blood administration in HS patients to avoid the MOF associated with reperfusion injury during resuscitation.

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“…HMEC‐1 (3 x 10 4 cells/well) cultured in 96‐well black plates were loaded, for 1 hour, with CM‐H 2 DCFDA (5 µmol/L) for analyzing intracellular ROS, or with DAF‐FM (5 µmol/L) for NO detection . After that, cells were pretreated or not with esculetin (10 µmol/L) or polymyxin B (25 µg/mL) for 15 minutes, and then treated with HPU (10 nmol/L) or buffer (control) for 30 minutes at 37ºC in a CO 2 air atmosphere.…”

Section: Methodsmentioning

confidence: 99%

Helicobacter pylori urease induces pro‐inflammatory effects and differentiation of human endothelial cells: Cellular and molecular mechanism

et al. 2019

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Background Helicobacter pylori urease (HPU) is a key virulence factor that enables bacteria to colonize and survive in the stomach. We early demonstrated that HPU, independent of its catalytic activity, induced inflammatory and angiogenic responses in vivo and directly activated human neutrophils to produce reactive oxygen species (ROS). We have investigated the effects of HPU on endothelial cells, focusing on the signaling mechanism involved. Methods Monolayers of human microvascular endothelial cells (HMEC‐1) were stimulated with HPU (up to 10 nmol/L): Paracellular permeability was accessed through dextran‐FITC passage. NO and ROS production was evaluated using intracellular probes. Proteins or mRNA expressions were detected by Western blotting and fluorescence microscopy or qPCR assays, respectively. Results Treatment with HPU enhanced paracellular permeability of HMEC‐1, preceded by VE‐cadherin phosphorylation and its dissociation from cell‐cell junctions. This caused profound alterations in actin cytoskeleton dynamics and focal adhesion kinase (FAK) phosphorylation. HPU triggered ROS and nitric oxide (NO) production by endothelial cells. Increased intracellular ROS resulted in nuclear factor kappa B (NF‐κB) activation and upregulated expression of cyclooxygenase‐2 (COX‐2), hemeoxygenase‐1 (HO‐1), interleukin‐1β (IL‐1β), and intercellular adhesion molecule‐1 (ICAM‐1). Higher ICAM‐1 and E‐selectin expression was associated with increased neutrophil adhesion on HPU‐stimulated HMEC monolayers. The effects of HPU on endothelial cells were dependent on ROS production and lipoxygenase pathway activation, being inhibited by esculetin. Additionally, HPU improved vascular endothelial growth factor receptor 2 (VEGFR‐2) expression. Conclusion The data suggest that the pro‐inflammatory properties of HPU drive endothelial cell to a ROS‐dependent program of differentiation that contributes to the progression of H pylori infection.

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Rapid NOS-1-derived nitric oxide and peroxynitrite formation act as signaling agents for inducible NOS-2 expression in vascular smooth muscle cells

Cited by 16 publications

References 56 publications

High Levels of Soluble Endoglin Induce a Proinflammatory and Oxidative-Stress Phenotype Associated with Preserved NO-Dependent Vasodilatation in Aortas from Mice Fed a High-Fat Diet

High Levels of Soluble Endoglin Induce a Proinflammatory and Oxidative-Stress Phenotype Associated with Preserved NO-Dependent Vasodilatation in Aortas from Mice Fed a High-Fat Diet

Neuronal Nitric Oxide Synthase is Involved in Vascular Hyporeactivity and Multiple Organ Dysfunction Associated with Hemorrhagic Shock

Helicobacter pylori urease induces pro‐inflammatory effects and differentiation of human endothelial cells: Cellular and molecular mechanism

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