Inhibition of factor Xa suppresses the expression of tissue factor in human monocytes and lipopolysaccharide-induced endotoxemia in rats

Akahane, Kazuhisa; Okamoto, Kohji; Kikuchi, Makoto; Todoroki, Hidekazu; Higure, Aiichiro; Ohuchida, Tomoko; Kitahara, Kohtaro; Takeda, Satoru; Itoh, Hideaki; Ohsato, Keiichi

doi:10.1067/msy.2001.116452

Cited by 30 publications

(30 citation statements)

References 36 publications

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“…PCR array analysis also detected altered gene expression for proteases and serpins (nonsignificant reductions in tPA and uPA and significant increases in fII, NSP, and PAI-1), which may extend this activity. Prior studies with antithrombin and drugs that inhibited only thrombosis or thrombolysis did not prove consistently beneficial (9,10,29). Treatment with fX inhibitors in animal models has also indicated a modest improvement in sepsis (35).…”

Section: Figmentioning

confidence: 99%

“…*, **, and ***, P Յ 0.05, P Ͻ 0.01, and P Ͻ 0.009, respectively. infection, with mouse-adapted Zaire ebolavirus (4,28,29), was also assessed, and in this mouse model, Serp-1 treatment again reduced viral load necrosis and inflammation and improved survival.…”

Section: Figmentioning

confidence: 99%

“…These differing infections were studied to determine the range of potential efficacy of viral immunomodulating serpin treatments. MHV-68 is widely used as a mouse model for Epstein Barr virus (EBV) and human herpesvirus 8 infections (27)(28)(29)35) and is a well-characterized rodent model for studying gammaherpesviruses. MHV68 infection in IFN-␥R-deficient mice provides an extension of this model, with a marked inflammatory cell response and hemorrhage providing a viral sepsis model.…”

Section: Figmentioning

confidence: 99%

“…The 1976 Mayinga isolate of ebolavirus from Zaire (now the Democratic Republic of the Congo) (4,28,29) was isolated from a human specimen on Vero E6 cells and passaged twice prior to initiation of these experiments. Focus-forming units (FFU) for Zaire ebolavirus were assayed by Ebola virus matrix protein (VP40)-specific antiserum.…”

Section: Ethics Statementmentioning

confidence: 99%

“…MHV68 serves as a recognized model for human inflammatory vasculitis and lethal herpesvirus infections. To assess for the capacity to alter the course of a second unrelated hemorrhagic lethal virus infection in wild-type mice, Serp-1 treatment of mouse-adapted Zaire ebolavirus, a category A virus (28,29), in BALB/c mice was also examined. MHV causes high mortality in IFN-␥R knockout mice but not in wild-type mice.…”

mentioning

confidence: 99%

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Myxomavirus-Derived Serpin Prolongs Survival and Reduces Inflammation and Hemorrhage in an Unrelated Lethal Mouse Viral Infection

Chen

Zheng

Abbott

et al. 2013

Antimicrob Agents Chemother

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Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Section: Ethics Statementmentioning

confidence: 99%

mentioning

confidence: 99%

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Myxomavirus-Derived Serpin Prolongs Survival and Reduces Inflammation and Hemorrhage in an Unrelated Lethal Mouse Viral Infection

Chen

Zheng

Abbott

et al. 2013

Antimicrob Agents Chemother

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Tissue factor upregulation drives a thrombosis–inflammation circuit in relation to cardiovascular complications

Chu

2006

Cell Biochem. Funct.

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The extrinsic coagulation is recognized as an 'inducible' signalling cascade resulting from tissue factor (TF) upregulation by exposure to clotting zymogen FVII upon inflammation or tissue injury. Following the substantial initiation, an array of proteolytic activation generates mediating signals (active serine proteases: FVIIa, FXa and FIIa) that lead to hypercoagulation with fibrin overproduction manifesting thrombosis. In addition, TF upregulation plays a central role in driving a thrombosis-inflammation circuit. Coagulant mediators (FVIIa, FXa and FIIa) and endproduct (fibrin) are proinflammatory, eliciting tissue necrosis factor, interleukins, adhesion molecules and many other intracellular signals in different cell types. Such resulting inflammation could ensure 'fibrin' thrombosis via feedback upregulation of TF. Alternatively, the resulting inflammation triggers platelet/leukocyte/polymononuclear cell activation thus contributing to 'cellular' thrombosis. TF is very vulnerable to upregulation resulting in hypercoagulability and subsequent thrombosis and inflammation, either of which presents cardiovascular risks. The prevention and intervention of TF hypercoagulability are of importance in cardioprotection. Blockade of inflammation reception and its intracellular signalling prevents TF expression from upregulation. Natural (activated protein C, tissue factor pathway inhibitor, or antithrombin III) or pharmacological anticoagulants readily offset the extrinsic hypercoagulation mainly through FVIIa, FXa or FIIa inhibition. Therefore, anticoagulants turn off the thrombosis-inflammation circuit, offering not only antithrombotic but anti-inflammatory significance in the prevention of cardiovascular complications.

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Factor Xa Signaling Contributes to the Pathogenesis of Inflammatory Diseases

Ebrahimi

Rezaei

Seiri

et al. 2016

Journal Cellular Physiology

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The coagulation protease Factor Xa (FXa) triggers a variety of signaling pathways through activation of protease-activated receptors (PARs) and non-PAR receptors. FXa-mediated signaling is strongly implicated in the pathogenesis of several inflammatory diseases including fibrosis, cardiovascular diseases, and cancer. Thus, targeting of FXa can have great clinical significance in terms of the treatment of these disorders. This review summarizes the current knowledge about the mechanism of FXa signaling in cellular and animal systems under (patho) physiological conditions for a better understanding and hence a better management of FXa-induced disorders. J. Cell. Physiol. 232: 1966-1970, 2017. © 2016 Wiley Periodicals, Inc.

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Inhibition of factor Xa suppresses the expression of tissue factor in human monocytes and lipopolysaccharide-induced endotoxemia in rats

Cited by 30 publications

References 36 publications

Myxomavirus-Derived Serpin Prolongs Survival and Reduces Inflammation and Hemorrhage in an Unrelated Lethal Mouse Viral Infection

Myxomavirus-Derived Serpin Prolongs Survival and Reduces Inflammation and Hemorrhage in an Unrelated Lethal Mouse Viral Infection

Tissue factor upregulation drives a thrombosis–inflammation circuit in relation to cardiovascular complications

Factor Xa Signaling Contributes to the Pathogenesis of Inflammatory Diseases

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