PMID- 15711752
OWN - NLM
STAT- MEDLINE
DCOM- 20050728
LR  - 20181201
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 93
IP  - 2
DP  - 2005 Feb
TI  - Fluvastatin increases the expression of adhesion molecules, monocyte 
      chemoattractant protein-1 and tissue factor in HUVEC stimulated by patient IgG 
      fractions containing antiphospholipid antibodies.
PG  - 339-45
AB  - 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).
FAU - Dunoyer-Geindre, Sylvie
AU  - Dunoyer-Geindre S
AD  - Unit of Haemostasis, University Hospital of Geneva, 24, Rue Micheli-du-Crest, 
      1211 Geneva 14, Switzerland, E-mail: philippe.demoerloose@hcuge.ch.
FAU - Dimitrova, Yordanka
AU  - Dimitrova Y
FAU - Fish, Richard J
AU  - Fish RJ
FAU - Satta, Nathalie
AU  - Satta N
FAU - Reber, Guido
AU  - Reber G
FAU - Kruithof, Egbert K O
AU  - Kruithof EK
FAU - de Moerloose, Philippe
AU  - de Moerloose P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Antibodies, Antiphospholipid)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Fatty Acids, Monounsaturated)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Indoles)
RN  - 4L066368AS (Fluvastatin)
RN  - 9035-58-9 (Thromboplastin)
SB  - IM
CIN - Thromb Haemost. 2005 Feb;93(2):186-8. PMID: 15711729
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Antiphospholipid/pharmacology
MH  - Antiphospholipid Syndrome/*pathology
MH  - Cell Adhesion Molecules/analysis/drug effects/*genetics
MH  - Cells, Cultured
MH  - Chemokine CCL2/analysis/drug effects/*genetics
MH  - Endothelium, Vascular/*drug effects/pathology
MH  - Fatty Acids, Monounsaturated/*pharmacology
MH  - Female
MH  - Fluvastatin
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Immunoglobulin G/pharmacology
MH  - Indoles/*pharmacology
MH  - Inflammation/chemically induced/immunology
MH  - Male
MH  - Middle Aged
MH  - Thromboplastin/analysis/drug effects/*genetics
MH  - Umbilical Cord/cytology
EDAT- 2005/02/16 09:00
MHDA- 2005/07/29 09:00
CRDT- 2005/02/16 09:00
PHST- 2005/02/16 09:00 [pubmed]
PHST- 2005/07/29 09:00 [medline]
PHST- 2005/02/16 09:00 [entrez]
AID - 05020339 [pii]
AID - 10.1160/TH04-05-0297 [doi]
PST - ppublish
SO  - Thromb Haemost. 2005 Feb;93(2):339-45. doi: 10.1160/TH04-05-0297.