Thrombogenic Properties of Murine Anti-Cardiolipin Antibodies Induced by β
            <sub>2</sub>
            Glycoprotein 1 and Human Immunoglobulin G Antiphospholipid Antibodies

Pierangeli, Silvia S.; Liu, Xiao Wei; Anderson, Garth; Barker, John H.; Harris, E. N.

doi:10.1161/01.cir.94.7.1746

Cited by 120 publications

(95 citation statements)

References 34 publications

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“…Monoclonal and polyclonal aPL antibodies have previously been demonstrated to have thrombogenic properties in mice (6,37,46,48). Several studies have demonstrated that aPL activate ECs in vitro, suggesting a mechanism by which these antibodies exert procoagulant properties (15,49,50).…”

Section: Discussionmentioning

confidence: 99%

“…Analysis of thrombus dynamics. The analysis of thrombus dynamics in a mouse model has been described previously (4)(5)(6)46). Briefly, mice were anesthetized at 72 hours after the first injection with IgG-APS or IgG-NHS.…”

Section: Methodsmentioning

confidence: 99%

“…Experimental evidence shows that antiphospholipid antibodies (aPL) not only are markers of the disease, but also may play a causative role in the development of vascular thrombosis and pregnancy morbidity (3)(4)(5)(6)(7)(8). Nonetheless, the pathogenic mechanisms of aPL seem to be heterogeneous and far from being completely understood (9).…”

Section: Conclusion These Findings Indicate That Fluvastatin Signifimentioning

confidence: 99%

“…To test this hypothesis, we used a previously devised mouse model of APS in which human polyclonal and monoclonal aCL antibodies have been demonstrated to increase the thrombus size induced by a standardized injury (4)(5)(6). We also used a microcirculation model of mouse cremaster muscle to study the effects of aPL on monocyte adherence to ECs (37).…”

Section: Conclusion These Findings Indicate That Fluvastatin Signifimentioning

confidence: 99%

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Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model

Ferrara¹,

Liu²,

Espinola³

et al. 2003

Arthritis & Rheumatism

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138

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Methods. Two groups of CD-1 male mice, each comprising ϳ18 mice, were fed either normal saline solution or 15 mg/kg fluvastatin for 15 days. Each of the 2 groups was further subdivided to receive either purified IgG from patients with the antiphospholipid syndrome (IgG-APS) or normal IgG from healthy subjects. Analysis of thrombus dynamics was performed in treated and control mice, using a standardized thrombogenic injury procedure, and the area (size) of the thrombus was measured. Adhesion of leukocytes to ECs was analyzed with a microcirculation model of exposed cremaster muscle. Baseline and posttreatment soluble intercellular adhesion molecule 1 (sICAM-1) levels were determined by enzyme-linked immunosorbent assay.Results. IgG-APS mice treated with fluvastatin showed significantly smaller thrombi, a reduced number of adherent leukocytes, and decreased levels of sICAM-1 compared with IgG-APS animals treated with placebo.Conclusion. These findings indicate that fluvastatin significantly diminishes aPL-mediated thrombosis and EC activation in vivo. These results may have important implications for the design of new treatment strategies aimed at preventing recurrent thrombosis in patients with APS.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Conclusion These Findings Indicate That Fluvastatin Signifimentioning

confidence: 99%

Section: Conclusion These Findings Indicate That Fluvastatin Signifimentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model

Ferrara¹,

Liu²,

Espinola³

et al. 2003

Arthritis & Rheumatism

Self Cite

138

View full text Add to dashboard Cite

show abstract

“…These autoantibodies are not only markers of APS, but also believed to play pathogenic roles in the development of symptoms in patients with APS (Pierangeli et al,1996;Tsutsumi et al,1996).…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis of antiphospholipid antibodies: impairment of fibrinolysis and monocyte activation via the p38 mitogen-activated protein kinase pathway

et al. 2005

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Antiphospholipid syndrome (APS) is characterized by recurrent thrombosis or pregnancy morbidity associated with antiphospholipid antibodies (aPL). Impaired fibrinolysis is a contributing factor for the development of thrombosis, and the effect of aPL in the fibrinolytic system has been investigated. Impaired release of tPA and enhanced release of PAI-1 after endothel activation is reported in patients with APS. Elevated Lipoprotein (a) levels have been found in APS, which results in inhibition of fibrinolytic activity. Phospholipid-bound β 2 -glycoprotein I (β 2 GPI) is a major autoantigen for aPLs. β2GPI exerts both anti-coagulant and pro-coagulant properties mainly by interacting with other phospholipid-binding proteins such as coagulation factors and protein C. Dramatic increase in the affinity of β 2 GPI to the cell surface is induced by binding of pathogenic anti-β 2 GPI antibodies, which may modify the physiological function of β 2 GPI and may affect the coagulation/fibrinolysis balance on the cell surface.Using chromogenic assays for measuring fibrinolytic activity, we demonstrated that addition of monoclonal anticardiolipin antibody (aCL) decreases the activity of extrinsic/intrinsic fibrinolysis. Significantly lower activity of intrinsic fibrinolysis was also demonstrated in the euglobulin fractions from APS patients.Endothelial cells and monocytes are activated by aPLs in vitro, resulting in production of tissue factor (TF), a major initiator of the coagulation system. Recently, aPLs are reported to induce thrombocytes to produce thromboxane. The importance of apoE receptor 2 on platelets for the binding of artificially-dimerized β 2 GPI was suggested. By investigating aPL-inducible genes in peripheral blood mononuclear cells, we found that mitogen-activated protein kinase (MAPK) pathway was up-regulated. Using monocyte cell line, phosphorylation of p38 MAPK, NF-κB 3 translocation to the nuclear fraction, and up-regulated TF mRNA expression were demonstrated after treatment with monoclonal aCL. These phenomena were observed only in the presence of β 2 GPI. Moreover, a specific p38 MAPK inihibitor SB203580 decreased aCL/β 2 GPI-induced TF mRNA expression.

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Ciprofloxacin immunomodulation of experimental antiphospholipid syndrome associated with elevation of interleukin‐3 and granulocyte‐macrophage colony‐stimulating factor expression

Blank

George

Fishman³

et al. 1998

Arthritis & Rheumatism

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Objective. To evaluate the immunomodulatory potential of ciprofloxacin in mice with experimental antiphospholipid syndrome (APS).Methods. Ciprofloxacin or ceftazidime (control antibiotic) was given to mice with experimentally induced APS. The titers of autoantibodies, levels of cytokines, and number of cytokine-producing cells were determined by enzyme-linked immunosorbent assay. Myeloid progenitor cells were determined by granulocyte-macrophage colony-forming unit, and interleukin-3 (IL-3) messenger RNA (mRNA) was tested by Northern analysis.Results. A decrease in the incidence of pregnancy loss and an improvement in the clinical manifestations of APS were noted in the mice treated with ciprofloxacin, compared with the mice given ceftazidime. The effect of ciprofloxacin was found to be associated with increased serum levels of IL-3 and with increased IL-3 mRNA transcription in the splenocytes. Expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was documented by elevated titers in the sera and elevated numbers of colony-forming cells in the bone marrow.

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Thrombogenic Properties of Murine Anti-Cardiolipin Antibodies Induced by β ₂ Glycoprotein 1 and Human Immunoglobulin G Antiphospholipid Antibodies

Abstract: Demonstration of a thrombogenic effect of murine anti-cardiolipin antibodies suggests that these antibodies may be pathogenic in humans with APS.

Cited by 120 publications

References 34 publications

Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model

Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model

Pathogenesis of antiphospholipid antibodies: impairment of fibrinolysis and monocyte activation via the p38 mitogen-activated protein kinase pathway

Ciprofloxacin immunomodulation of experimental antiphospholipid syndrome associated with elevation of interleukin‐3 and granulocyte‐macrophage colony‐stimulating factor expression

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Thrombogenic Properties of Murine Anti-Cardiolipin Antibodies Induced by β 2 Glycoprotein 1 and Human Immunoglobulin G Antiphospholipid Antibodies

Abstract: Demonstration of a thrombogenic effect of murine anti-cardiolipin antibodies suggests that these antibodies may be pathogenic in humans with APS.

Cited by 120 publications

References 34 publications

Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model

Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model

Pathogenesis of antiphospholipid antibodies: impairment of fibrinolysis and monocyte activation via the p38 mitogen-activated protein kinase pathway

Ciprofloxacin immunomodulation of experimental antiphospholipid syndrome associated with elevation of interleukin‐3 and granulocyte‐macrophage colony‐stimulating factor expression

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Thrombogenic Properties of Murine Anti-Cardiolipin Antibodies Induced by β ₂ Glycoprotein 1 and Human Immunoglobulin G Antiphospholipid Antibodies