Fluvastatin increases the expression of adhesion molecules, monocyte chemoattractant protein-1 and tissue factor in HUVEC stimulated by patient IgG fractions containing antiphospholipid antibodies

Article Article professionnel Article Fluvastatin increases the expression of adhesion molecules, monocyte chemoattractant protein-1 and tissue factor in HUVEC stimulated by patient IgG fractions containing antiphospholipid antibodies eng 2005 author Geindre Sylvie Françoise 133391 author Dimitrova-tirefort Yordanka 544863 author Fish Richard 0000-0003-2830-4260 133844 author Satta Poschung Nathalie 134524 author Reber Guido 99164 author Kruithof Egbert 117791 author De Moerloose Philippe 26335 339-345 10.1267/THRO05020339 15711752 0340-6245 The presence of antiphospholipid antibodies (APLA) is associated with an increased risk of recurrent thrombosis and pregnancy loss. APLA are able to activate endothelial cells (EC) and induce an increase in the expression of inflammatory marker proteins, such as leukocyte adhesion molecules, tissue factor or the monocyte chemoattractant protein-1 (MCP-1). Our objective was to investigate the effect of statins on EC activation induced by APLA in vitro. IgG was purified from the plasma of six patients with APLA and from healthy controls. EC were incubated with patient IgG or with control IgG, in the presence or absence of 5microM of fluvastatin, and expression of the leukocyte adhesion molecules, VCAM-1 and E-selectin, analyzed by flow cytometry and by quantitative reverse transcriptase-PCR (QRT-PCR). The expression of tissue factor and the chemokine MCP-1 was analyzed by QRT-PCR alone. Incubation of EC with patient IgG increased the expression of VCAM-1, E-selectin, tissue factor and MCP-1. Prior treatment of the cells with fluvastatin further increased the expression of these proteins. The fluvastatin effect was reversed by co-incubation with mevalonate or geranylgeranylpyrophosphate and mimicked by the geranylgeranyl transferase inhibitor GGTI-286. Our results show that in cultured human EC, statins increase the extent of inflammatory activation induced by APLA. This effect appears to be mediated by an inhibitory effect of statins on one or more geranylgeranylated protein(s). Adolescent Adult Antibodies, Antiphospholipid/pharmacology Antiphospholipid Syndrome/pathology Cell Adhesion Molecules/analysis/drug effects/genetics Cells, Cultured Chemokine CCL2/analysis/drug effects/genetics Endothelium, Vascular/drug effects/pathology Fatty Acids, Monounsaturated/pharmacology Female Gene Expression Regulation/drug effects Humans Immunoglobulin G/pharmacology Indoles/pharmacology Inflammation/chemically induced/immunology Male Middle Aged Thromboplastin/analysis/drug effects/genetics Umbilical Cord/cytology Dewey 616 56 Département de médecine 221 false Thrombosis and haemostasis 93 2 d10e8b14-57b0-428b-84e7-95399f4f7ffa Article (Published version) Public Dunoyer Geindre TH 2005 339.pdf 305462 application/pdf openAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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Fluvastatin increases the expression of adhesion molecules, monocyte chemoattractant protein-1 and tissue factor in HUVEC stimulated by patient IgG fractions containing antiphospholipid antibodies	Thrombosis and haemostasis			2005	714	400

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