Role of Oxygen Radicals in Tissue Factor Induction by Endotoxin in Blood Monocytes

Polack, Benoı̂t; Pernod, Gilles; Barro, Claire; Doussière, Jacques

doi:10.1159/000217456

Cited by 18 publications

(20 citation statements)

References 23 publications

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“…29 -31 Upregulation of tissue factor may also be facilitated by O 2 ⅐Ϫ . 34 Consistent with these ideas, we have recently reported that AF is associated with a downregulation of LAA NO ⅐ and increases in PAI-1 and tissue factor. 12,35 Our data suggest that the NAD(P)H oxidase is responsible for at least some of the O 2 ⅐Ϫ produced by the atria in AF.…”

Section: Our Data Indicate That the Increase In Osupporting

confidence: 66%

Atrial Fibrillation Increases Production of Superoxide by the Left Atrium and Left Atrial Appendage

et al. 2005

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Background— Atrial fibrillation (AF) is associated with an increased risk of stroke due almost exclusively to emboli from left atrial appendage (LAA) thrombi. Recently, we reported that AF was associated with endocardial dysfunction, limited to the left atrium (LA) and LAA and manifest as reduced nitric oxide (NO · ) production and increased expression of plasminogen activator inhibitor-1. We hypothesized that reduced LAA NO · levels observed in AF may be associated with increased superoxide (O 2 ·− ) production. Methods and Results— After a week of AF induced by rapid atrial pacing in pigs, O 2 ·− production from acutely isolated heart tissue was measured by 2 independent techniques, electron spin resonance and superoxide dismutase–inhibitable cytochrome C reduction assays. Compared with control animals with equivalent ventricular heart rates, basal O 2 ·− production was increased 2.7-fold ( P <0.01) and 3.0-fold ( P <0.02) in the LA and LAA, respectively. A similar 3.0-fold ( P <0.01) increase in LAA O 2 ·− production was observed using a cytochrome C reduction assay. The increases could not be explained by changes in atrial total superoxide dismutase activity. Addition of either apocyanin or oxypurinol reduced LAA O 2 ·− , implying that NADPH and xanthine oxidases both contributed to increased O 2 ·− production in AF. Enzyme assays of atrial tissue homogenates confirmed increases in LAA NAD(P)H oxidase ( P =0.04) and xanthine oxidase ( P =0.01) activities. Although there were no changes in expression of the NADPH oxidase subunits, the increase in superoxide production was accompanied by an increase in GTP-loaded Rac1, an activator of the NADPH oxidase. Conclusions— AF increased O 2 ·− production in both the LA and LAA. Increased NAD(P)H oxidase and xanthine oxidase activities contributed to the observed increase in LAA O 2 ·− production. This increase in O 2 ·− and its reactive metabolites may contribute to the pathological consequences of AF such as thrombosis, inflammation, and tissue remodeling.

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Section: Our Data Indicate That the Increase In Osupporting

confidence: 66%

Atrial Fibrillation Increases Production of Superoxide by the Left Atrium and Left Atrial Appendage

et al. 2005

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“…In contrast, the antioxidants PDTC and N-acetyl cysteine (NAC) inhibit LPS induction of inflammatory genes and TF in monocytes, macrophages, and endothelial cells by reducing NF-B activation. 6,21,22,31,35,36 These results indicate that AGI-1067 and AGI-1095 inhibit LPS induction of gene expression via a mechanism that is distinct from other antioxidant compounds, such as PDTC and NAC ( Figure 6). Other antioxidant compounds (ie, flavanoids) also do not inhibit inducible NF-B activation 37,38 despite their ability to inhibit inflammatory gene expression in endothelial cells.…”

Section: Discussionmentioning

confidence: 91%

A Novel Class of Antioxidants Inhibit LPS Induction of Tissue Factor by Selective Inhibition of the Activation of ASK1 and MAP Kinases

Luyendyk

Piper

Tencati

et al. 2007

ATVB

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Objective-Oxidative stress contributes to the pathogenesis of many diseases, including atherosclerosis and sepsis. We have previously described a novel class of therapeutic compounds with antioxidant and antiinflammatory properties. However, at present, the intracellular targets of these compounds have not been identified. The purpose of this study was to elucidate the mechanism by which 2 structurally-related antioxidants (AGI-1067 and AGI-1095) inhibit LPS induction of tissue factor (TF) expression in human monocytic cells and endothelial cells. Methods and Results-We found that succinobucol (AGI-1067) and AGI-1095 inhibited LPS induction of TF expression in both monocytic cells and endothelial cells. These compounds also reduced LPS induction of nuclear AP-1 and expression of Egr-1 without affecting nuclear translocation of NF-B. Importantly, these antioxidants inhibited LPS activation of the redox-sensitive kinase, apoptosis signal-regulating kinase-1 (ASK1) and the mitogen-activated protein kinases (MAPKs) p38, ERK1/2, and JNK1/2. Conclusions-AGI-1067 and AGI-1095 inhibit TF gene expression in both monocytic cells and endothelial cells through a mechanism that involves the inhibition of the redox-sensitive MAP3K, ASK1. These compounds selectively reduce the activation/induction of MAPK, AP-1, and Egr-1 without affecting NF-B nuclear translocation. (Arterioscler Thromb

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“…Superoxide anions participate in the induction of TF at the surface of blood monocytes stimulated by LPS [26] and are involved in the upregulation of TF in vascular smooth muscle cells in response to activated platelets [9]. Via the release of superoxide anions, polymorphonuclear leukocytes modulate TF production by mononuclear cells [6].…”

Section: Discussionmentioning

confidence: 99%

Scoparone Inhibits Tissue Factor Expression in Lipopolysaccharide-Activated Human Umbilical Vein Endothelial Cells

Lee¹,

Hsiao²,

Chang³

et al. 2003

J Biomed Sci

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Tissue factor (TF) is an important regulator and effector molecule of coagulation in various inflammatory states. In sepsis, expression of TF by activated endothelial cells leads to disseminated intravascular coagulation. Scoparone is extracted from the traditional Chinese herb Artemisia scoparia and is known to have potent anti-inflammatory properties. In the current studies, we examined the effects of scoparone on inhibiting lipopolysaccharide (LPS)-induced TF expression in cultured human umbilical vein endothelial cells (HUVECs). Flow-cytometric analysis revealed LPS (10 µg/ml)-activated surface TF induction was concentration-dependently inhibited by scoparone (10–400 µM). The concentrations of scoparone used in this study did not affect cell viability. The elevation of the procoagulant activity of TF by LPS was suppressed by scoparone. The LPS-induced superoxide formation was markedly decreased by scoparone. Messenger RNA expression of TF in LPS-activated HUVECs was also reduced by scoparone. Furthermore, scoparone did not significantly affect the IĸBα degradation. Our results demonstrate that the inhibition of scoparone on LPS-induced TF expression in HUVECs may mediate by the mechanisms suppressing superoxide anion formation and TF transcription.

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Role of Oxygen Radicals in Tissue Factor Induction by Endotoxin in Blood Monocytes

Cited by 18 publications

References 23 publications

Atrial Fibrillation Increases Production of Superoxide by the Left Atrium and Left Atrial Appendage

Atrial Fibrillation Increases Production of Superoxide by the Left Atrium and Left Atrial Appendage

A Novel Class of Antioxidants Inhibit LPS Induction of Tissue Factor by Selective Inhibition of the Activation of ASK1 and MAP Kinases

Scoparone Inhibits Tissue Factor Expression in Lipopolysaccharide-Activated Human Umbilical Vein Endothelial Cells

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