Antioxidative treatment inhibits the release of thrombogenic tissue factor from irradiation- and cytokine-induced endothelial cells

Szotowski, Björn; Antoniak, Silvio; Goldin-Lang, Petra; Tran, Quoc-Viet; Pels, Klaus; Rosenthal, Peter; Bogdanov, Vladimir Y.; Borchert, Hans-Hubert; Schultheiss, Heinz‐Peter; Rauch, Ursula

doi:10.1016/j.cardiores.2006.12.018

Cited by 75 publications

(50 citation statements)

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“…Combes et al firstly described the generation of EMP from human umbilical vein endothelial cells stimulated by TNF-␣. 4 Besides TNF-␣, other inflammatory cytokines 18 and also bacterial lipopolysaccharides, reactive oxygen species, 18 plasminogen activator inhibitor, 19 thrombin, 20 camptothecin, 21 C-reactive protein, 22 and uremic toxins 23 are able to induce in vitro EMP generation. Interestingly, endogenous nitric oxide dampens the release of EMP on stimulation with C-reactive protein by a mechanism involving tetrahydrobiopterin 22 (Figure 3).…”

Section: Mechanisms Of Emp Formationmentioning

confidence: 99%

The Many Faces of Endothelial Microparticles

Dignat-George

Boulanger

2011

ATVB

544

495

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Abstract-Endothelial microparticles (EMP) are complex vesicular structures shed from activated or apoptotic endothelial cells. They play a remarkable role in coagulation, inflammation, endothelial function, and angiogenesis and thus disturb the vascular homeostasis, contributing to the progression of vascular diseases. As a cause or a consequence, elevated levels of EMP were found in plasma from patients with vascular diseases, where they serve as a surrogate marker of endothelial function. More recent data challenged the presumed deleterious role of EMP because they could promote cell survival, exert antiinflammatory effects, counteract coagulation processes, or induce endothelial regeneration. This review focuses on the ambivalent role of EMP in vascular homeostasis. (Arterioscler Thromb Vasc Biol. 2011;31:27-33.)Key Words: apoptosis Ⅲ atherosclerosis Ⅲ endothelial function Ⅲ endothelium Ⅲ thrombin Ⅲ thrombosis Ⅲ vascular biology Ⅲ microparticles V ascular endothelial cells, like most cells, release different types of membrane vesicles, including microparticles (MP) and exosomes, in response to cellular activation or apoptosis. In addition, apoptotic bodies might be generated during the final steps of programmed cell death. These different vesicles are distinguished from one another on the basis of their subcellular origin, their size, their content, the mechanisms leading to their formation, and, from a practical point of view, how they are obtained. Endothelial Microparticle CharacteristicsEndothelial microparticles (EMP) (Ϸ100 nm to 1 m in diameter) result from endothelial plasma membrane blebbing and carry endothelial proteins such as vascular endothelial cadherin, platelet endothelial cell adhesion molecule-1, intercellular cell adhesion molecule (ICAM)-1, endoglin, E-selectin, S-endo or ␣v integrin (Figure 1). 1 Endothelial NO synthase and vascular endothelial growth factor receptor (VEGF-R2) have also been identified on EMP, 2 but there is so far no evidence on whether or not MP endothelial nitric oxide synthase is capable of generating nitric oxide; furthermore, endothelial nitric oxide synthase may also be present on platelet or red blood cell-derived MP. E-selectin (CD62E) is expressed by activated endothelial cells but can equally be found on EMP generated following either tumor necrosis factor-␣ (TNF-␣) activation or growth factor deprivationinduced apoptosis. 3 Identification of endothelial origin of circulating MP relies on the use of specific markers for flow cytometry analysis (see below); unfortunately, except E-selectin and vascular endothelial cadherin, most of them lack exclusive endothelial expression. Endoglin (CD105) is also expressed by activated monocytes/macrophages and bone marrow cell subsets; platelet endothelial cell adhesion molecule-1 (CD31) is present on activated platelets, platelet MP, and leukocyte subsets; S-endo (CD146) has been found on pericytes, tumor cells, and activated T-cells; ICAM-1 (CD54) is also expressed by leukocytes; and ␣v integrin (CD51) is present on monocy...

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Section: Mechanisms Of Emp Formationmentioning

confidence: 99%

The Many Faces of Endothelial Microparticles

Dignat-George

Boulanger

2011

ATVB

544

495

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“…Antioxidative treatment inhibits the release of thrombogenic TF from irradiation-and cytokinetreated ECs, indicating a significant role of endothelial ROS in thrombotic regulation. 56 Furthermore, endothelial-specific deletion of Txnrd2, an enzyme negatively regulates the levels of mitochondrial ROS, robustly enhances fibrin deposition. 57 In line with this study, Li et al 58 showed that mitochondrial ROS was responsible for lysophosphatidylcholine-induced EC activation.…”

Section: Reactive Oxygen Speciesmentioning

confidence: 99%

Thrombotic Regulation From the Endothelial Cell Perspectives

Wang

Hao

Leeper

et al. 2018

ATVB

121

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“…[1][2][3][4] Endothelial cells are crucial regulators of vascular wall homeostasis and blood thrombogenicity; 5-7 the inflammatory cytokine tumor necrosis factor (TNF)-α has been shown to induce the expression of 2 TF isoforms: membrane-bound human "full length" TF (flTF), [8][9][10] and a soluble alternatively spliced human TF (asHTF). 6,10,11 Both TF isoforms circulate in blood. 6,12 Fully active flTF appears to be the major source of the thrombogenicity of blood in a cancer setting.…”

mentioning

confidence: 99%

Role of the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway in Regulating Alternative Splicing of Tissue Factor mRNA in Human Endothelial Cells

Eisenreich

Malz

Pepke

et al. 2009

Circ J

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Background: Tissue factor (TF) is the primary initiator of blood coagulation. In response to tumor necrosis factor (TNF)-α human umbilical vein endothelial cells (HUVECs) express 2 TF isoforms: a soluble alternatively spliced isoform (asHTF) and membrane-bound "full length" (fl)TF. How the differential TF isoform expression is regulated is still unknown. This study compared the impact of PI3K/Akt pathway inhibition on alternative splicing of TF in HUVECs, to the influence of transcriptional regulation by inhibiting nuclear factor κ B (NFκB). Methods and Results:The mRNA expression of TF isoforms was assessed by real-time PCR, the thrombogenic activity was measured by a chromogenic TF activity assay and the phosphorylation state of serine/arginine-rich (SR) proteins was analyzed by western blotting. Transfection of HUVECs was done 72 h before the inhibition experiments were performed. PI3K/Akt pathway inhibition reduced the mRNA expression of asHTF but not flTF. Inhibition of NFκB reduced the expression of both isoforms. Moreover, the PI3K/Akt pathway inhibition, but not that of NFκB, modified the phosphorylation of the SR proteins SRp75, SRp55 and SF2/ASF. Additionally, overexpression of SF2/ASF and SRp75 influenced the differential TF-isoform expression in HUVECs. Conclusions: The PI3K/Akt pathway modulates alternative splicing of TF in HUVECs, distinct from transcriptional regulation. (Circ J 2009; 73: 1746 -1752

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Antioxidative treatment inhibits the release of thrombogenic tissue factor from irradiation- and cytokine-induced endothelial cells

Abstract: Antioxidative treatment inhibited apoptosis and shedding of microparticles, thereby reducing thrombogenicity. Thus, antioxidants may help to prevent late thrombosis after antiproliferative treatment when used in combination with anticoagulants.

Cited by 75 publications

References 50 publications

The Many Faces of Endothelial Microparticles

The Many Faces of Endothelial Microparticles

Thrombotic Regulation From the Endothelial Cell Perspectives

Role of the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway in Regulating Alternative Splicing of Tissue Factor mRNA in Human Endothelial Cells

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