Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model
Article first published online: 4 NOV 2003
Copyright © 2003 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 48, Issue 11, pages 3272–3279, November 2003
How to Cite
Ferrara, D. E., Liu, X., Espinola, R. G., Meroni, P. L., Abukhalaf, I., Harris, E. N. and Pierangeli, S. S. (2003), Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model. Arthritis & Rheumatism, 48: 3272–3279. doi: 10.1002/art.11449
- Issue published online: 4 NOV 2003
- Article first published online: 4 NOV 2003
- Manuscript Accepted: 28 JUL 2003
- Manuscript Received: 29 JUL 2002
- RCMI-NIH. Grant Number: G12-RR03034
- NIH-MBRS. Grant Number: GM-58268-02
Antiphospholipid antibodies (aPL) have thrombogenic properties in vivo, through their interactions with soluble coagulation factors and their ability to modulate the functions of cells involved in coagulation homeostasis. These antibodies have also been shown to enhance the adhesion of leukocytes to endothelial cells (ECs) in vivo. New lipophilic statins such as fluvastatin have antiinflammatory and antithrombogenic effects. This study uses an in vivo mouse model to investigate whether fluvastatin has an effect on decreasing both the adhesion of leukocytes to ECs and the thrombus formation induced by aPL.
Two groups of CD-1 male mice, each comprising ∼18 mice, were fed either normal saline solution or 15 mg/kg fluvastatin for 15 days. Each of the 2 groups was further subdivided to receive either purified IgG from patients with the antiphospholipid syndrome (IgG-APS) or normal IgG from healthy subjects. Analysis of thrombus dynamics was performed in treated and control mice, using a standardized thrombogenic injury procedure, and the area (size) of the thrombus was measured. Adhesion of leukocytes to ECs was analyzed with a microcirculation model of exposed cremaster muscle. Baseline and posttreatment soluble intercellular adhesion molecule 1 (sICAM-1) levels were determined by enzyme-linked immunosorbent assay.
IgG-APS mice treated with fluvastatin showed significantly smaller thrombi, a reduced number of adherent leukocytes, and decreased levels of sICAM-1 compared with IgG-APS animals treated with placebo.
These findings indicate that fluvastatin significantly diminishes aPL-mediated thrombosis and EC activation in vivo. These results may have important implications for the design of new treatment strategies aimed at preventing recurrent thrombosis in patients with APS.