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 language | English |
|---|---|
| Pages (from-to) | 1558-1563 |
| Number of pages | 6 |
| Journal | Journal of Thrombosis and Haemostasis |
| Volume | 2 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 2004 |
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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 journal › Article
}
TY - JOUR
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.
PY - 2004/9
Y1 - 2004/9
N2 - 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.
AB - 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.
KW - Antiphospholipid antibodies
KW - Antiphospholipid syndrome
KW - Statins
KW - Thrombosis
KW - Tissue factor
UR - http://www.scopus.com/inward/record.url?scp=7244237671&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=7244237671&partnerID=8YFLogxK
U2 - 10.1111/j.1538-7836.2004.00896.x
DO - 10.1111/j.1538-7836.2004.00896.x
M3 - Article
C2 - 15333031
AN - SCOPUS:7244237671
VL - 2
SP - 1558
EP - 1563
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
SN - 1538-7933
IS - 9
ER -