en
Professional article
Open access
English

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

Published inThrombosis and haemostasis, vol. 93, no. 2, p. 339-345
Publication date2005
Abstract

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).

Keywords
  • 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
Citation (ISO format)
GEINDRE, Sylvie Françoise et al. Fluvastatin increases the expression of adhesion molecules, monocyte chemoattractant protein-1 and tissue factor in HUVEC stimulated by patient IgG fractions containing antiphospholipid antibodies. In: Thrombosis and haemostasis, 2005, vol. 93, n° 2, p. 339–345. doi: 10.1267/THRO05020339
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal0340-6245
623views
228downloads

Technical informations

Creation04/11/2014 2:22:00 PM
First validation04/11/2014 2:22:00 PM
Update time03/14/2023 9:10:32 PM
Status update03/14/2023 9:10:32 PM
Last indexation10/18/2023 6:31:32 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack