Fluvastatin inhibits up-regulation of tissue factor expression by antiphospholipid antibodies on endothelial cells

D. E. Ferrara, R. Swerlick, K. Casper, P. L. Meroni, M. E. Vega-Ostertag, E. N. Harris, S. S. Pierangeli

Research output: Contribution to journalArticle

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Abstract

Background: Mechanisms of thrombosis induced by antiphospholipid (aPL) antibodies include up-regulation of tissue factor (TF) expression on endothelial cells (ECs). Statins have been shown to reduce levels of TF induced by tumor necrosis factor (TNF-α) and lipopolysaccharide (LPS) on ECs. In a recent study, fluvastatin inhibited thrombogenic and proinflammatory properties of aPL antibodies in in vivo models. The aim of this study was to determine whether fluvastatin has an effect on aPL-induced expression of TF on ECs. Methods: IgGs were purified from four patients with APS (IgG-APS) and from control sera (IgG-NHS). Cultured human umbilical vein endothelial cells (HUVEC) were treated with IgG-APS or IgG-NHS or with medium alone or with phorbol myristate acetate (PMA), as a positive control. In some experiments, cells were pretreated with fluvastatin (2.5, 5 or 10 μM) with and without mevalonate (100 μM). TF expression on HLJVECs was measured by ELISA. Results: PMA and the four IgG-APS preparations increased the expression of TF on EC significantly (4.9-, 2.4-, 4.2-, 3.5- and 3.1-fold, respectively), in a dose-dependent fashion. Fluvastatin (10 μM) inhibited the effects of PMA and the four IgG-APS on TF expression by 70, 47, 65, 22 and 68%, respectively, and this effect was dose-dependent. Mevalonate (100 μM) completely abrogated the inhibitory effects of fluvastatin on TF expression induced by aPL. Conclusion: Because of the suggested pathogenic role of aPL on induction of TF on ECs, our data provide a rationale for using statins as a therapeutic tool in treatment of thrombosis in APS.

Original languageEnglish
Pages (from-to)1558-1563
Number of pages6
JournalJournal of Thrombosis and Haemostasis
Volume2
Issue number9
DOIs
Publication statusPublished - Sep 2004

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fluvastatin
Antiphospholipid Antibodies
Thromboplastin
Up-Regulation
Endothelial Cells
Immunoglobulin G
Tetradecanoylphorbol Acetate
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Mevalonic Acid
Thrombosis
Human Umbilical Vein Endothelial Cells

Keywords

  • Antiphospholipid antibodies
  • Antiphospholipid syndrome
  • Statins
  • Thrombosis
  • Tissue factor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Fluvastatin inhibits up-regulation of tissue factor expression by antiphospholipid antibodies on endothelial cells. / Ferrara, D. E.; Swerlick, R.; Casper, K.; Meroni, P. L.; Vega-Ostertag, M. E.; Harris, E. N.; Pierangeli, S. S.

In: Journal of Thrombosis and Haemostasis, Vol. 2, No. 9, 09.2004, p. 1558-1563.

Research output: Contribution to journalArticle

Ferrara, D. E. ; Swerlick, R. ; Casper, K. ; Meroni, P. L. ; Vega-Ostertag, M. E. ; Harris, E. N. ; Pierangeli, S. S. / Fluvastatin inhibits up-regulation of tissue factor expression by antiphospholipid antibodies on endothelial cells. In: Journal of Thrombosis and Haemostasis. 2004 ; Vol. 2, No. 9. pp. 1558-1563.
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abstract = "Background: Mechanisms of thrombosis induced by antiphospholipid (aPL) antibodies include up-regulation of tissue factor (TF) expression on endothelial cells (ECs). Statins have been shown to reduce levels of TF induced by tumor necrosis factor (TNF-α) and lipopolysaccharide (LPS) on ECs. In a recent study, fluvastatin inhibited thrombogenic and proinflammatory properties of aPL antibodies in in vivo models. The aim of this study was to determine whether fluvastatin has an effect on aPL-induced expression of TF on ECs. Methods: IgGs were purified from four patients with APS (IgG-APS) and from control sera (IgG-NHS). Cultured human umbilical vein endothelial cells (HUVEC) were treated with IgG-APS or IgG-NHS or with medium alone or with phorbol myristate acetate (PMA), as a positive control. In some experiments, cells were pretreated with fluvastatin (2.5, 5 or 10 μM) with and without mevalonate (100 μM). TF expression on HLJVECs was measured by ELISA. Results: PMA and the four IgG-APS preparations increased the expression of TF on EC significantly (4.9-, 2.4-, 4.2-, 3.5- and 3.1-fold, respectively), in a dose-dependent fashion. Fluvastatin (10 μM) inhibited the effects of PMA and the four IgG-APS on TF expression by 70, 47, 65, 22 and 68{\%}, respectively, and this effect was dose-dependent. Mevalonate (100 μM) completely abrogated the inhibitory effects of fluvastatin on TF expression induced by aPL. Conclusion: Because of the suggested pathogenic role of aPL on induction of TF on ECs, our data provide a rationale for using statins as a therapeutic tool in treatment of thrombosis in APS.",
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T1 - Fluvastatin inhibits up-regulation of tissue factor expression by antiphospholipid antibodies on endothelial cells

AU - Ferrara, D. E.

AU - Swerlick, R.

AU - Casper, K.

AU - Meroni, P. L.

AU - Vega-Ostertag, M. E.

AU - Harris, E. N.

AU - Pierangeli, S. S.

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