Endothelial Activation by aPL: A Potential Pathogenetic Mechanism for the Clinical Manifestations of the Syndrome

Meroni, Pier Luigi; Raschi, Elena; Camera, Marina; Testoni, Cinzia; Nicoletti, Ferdinando; Tincani, Anǵela; Khamashta, Munther A.; Balestrieri, G.; Tremoli, Elena; Hess, David C.

doi:10.1006/jaut.2000.0412

Cited by 134 publications

(88 citation statements)

References 35 publications

(21 reference statements)

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“…54). Also, Meroni et al (55) recently demonstrated that enhanced E-selectin expression by anti-␤ 2 gpI Abs in HUVEC is associated with NF-B activation. In our preliminary study, we observed that treatment with antioxidant pyrrolidine dithiocarbamate, a well-known inhibitor of NF-B, significantly abrogated the aPL-induced up-regulation of MCP-1 (data not shown).…”

Section: Discussionmentioning

confidence: 98%

Antiphospholipid Antibodies Induce Monocyte Chemoattractant Protein-1 in Endothelial Cells

Cho

Chen

et al. 2002

The Journal of Immunology

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The presence of antiphospholipid Ab is associated with increased risk of thrombosis. The monocyte-endothelial cell interaction has been suggested to play a key role at the site of vascular injury during thrombosis. Therefore, we tested the effect of anticardiolipin Abs (aCL) on the production of monocyte chemoattractant protein-1 (MCP-1) in HUVEC. We found that monoclonal aCL as well as IgG fractions from patients with antiphospholipid syndrome (APS-IgG) could induce the production of MCP-1 in HUVEC. The ability of IgG aCL to induce MCP-1 production could be abrogated by preabsorption with cardiolipin liposomes. Simultaneous addition of either monoclonal aCL or APS-IgG with IL-1β resulted in synergistic increase in MCP-1 production, whereas the addition of control IgG lacking aCL activity did not alter IL-1β-induced levels of MCP-1. MCP-1 mRNA expression was also up-regulated when HUVEC were incubated with either APS-IgG or monoclonal aCL, and down-regulated by the treatment of dexamethasone. In addition, we found that serum levels of MCP-1 in 76 systemic lupus erythematosus patients correlated well with the titers of IgG aCL. Collectively, these results indicate that aCL could promote endothelial cell-monocyte cross-talk by enhancing the endothelial production of MCP-1, thereby shifting the hemostatic balance toward the prothrombotic state of APS.

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Section: Discussionmentioning

confidence: 98%

Antiphospholipid Antibodies Induce Monocyte Chemoattractant Protein-1 in Endothelial Cells

Cho

Chen

et al. 2002

The Journal of Immunology

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“…Nonetheless, the pathogenic mechanisms of aPL seem to be heterogeneous and far from being completely understood (9). Among the mechanisms suggested to explain the prothrombotic activity of aPL are the direct inhibition of the activated protein C pathway (10), abnormalities in platelet function (11,12), up-regulation of the tissue factor pathway (13), and activation of endothelial cells (ECs) (14).…”

Section: Conclusion These Findings Indicate That Fluvastatin Signifimentioning

confidence: 99%

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

137

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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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“…84 -86 Cultured endothelial cells incubated with aPL antibodies express increased levels of cell adhesion molecules, 87 an effect that is mediated by ␤ 2 GPI, 88 and may increase the adhesion of leukocytes to the vascular wall and promote inflammation and thrombosis. Thrombogenic effects of aPL antibodies are mediated by intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin.…”

Section: Effects Of Apl Antibodies On Vascular Endothelial Cellsmentioning

confidence: 99%

Molecular Pathogenesis of the Antiphospholipid Syndrome

Rand

2002

Circulation Research

119

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Abstract-The antiphospholipid (aPL) syndrome is an acquired autoimmune disorder of unknown etiology in which patients present with thrombosis together with laboratory evidence for antibodies in blood that recognize anionic phospholipid-protein complexes. The main antigenic target for the aPL antibodies has been identified to be ␤ 2 glycoprotein I (␤ 2 GPI), a phospholipid-binding protein. The high affinity of aPL antibody-␤ 2 GPI complex for phospholipid membranes seems to be a critical step in the mechanism of this disease. This review focuses on some of the major mechanisms that have been proposed to explain this disorder. (Circ Res. 2002;90:29-37.)

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Endothelial Activation by aPL: A Potential Pathogenetic Mechanism for the Clinical Manifestations of the Syndrome

Cited by 134 publications

References 35 publications

Antiphospholipid Antibodies Induce Monocyte Chemoattractant Protein-1 in Endothelial Cells

Antiphospholipid Antibodies Induce Monocyte Chemoattractant Protein-1 in Endothelial Cells

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

Molecular Pathogenesis of the Antiphospholipid Syndrome

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