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Ann Rheum Dis. 2011 Apr;70(4):675-82. doi: 10.1136/ard.2010.135525. Epub 2010 Dec 20.

Global effects of fluvastatin on the prothrombotic status of patients with antiphospholipid syndrome.

Author information

1
IMIBIC, Hospital Reina Sofía, Avenida Menéndez Pidal s/n, E-14004 Córdoba, Spain. rosario.lopez.exts@juntadeandalucia.es

Abstract

OBJECTIVE:

Numerous mechanisms have been proposed to explain the thrombotic/proinflammatory tendency of antiphospholipid syndrome (APS) patients. Prothrombotic monocyte activation by antiphospholipid antibodies involves numerous proteins and intracellular pathways. The anti-inflammatory, anticoagulant and immunoregulatory effects of statins have been aimed as a therapeutic tool in APS patients. This study delineates the global effects of fluvastatin on the prothrombotic tendency of monocytes from APS patients.

METHODS:

Forty-two APS patients with thrombosis and 35 healthy donors were included in the study. APS patients received 20 mg/day fluvastatin for 1 month. Blood samples were obtained before the start, at the end and 2 months after the end of treatment.

RESULTS:

After 1 month of treatment, monocytes showed a significant inhibition of tissue factor, protein activator receptors 1 and 2, vascular endothelial growth factor and Flt1 expression that was related to the inhibition of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B/Rel DNA-binding activity. Proteomic analysis showed proteins involved in thrombotic development (annexin II, RhoA and protein disulphide isomerase) with altered expression after fluvastatin administration. In-vitro studies indicated that the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by fluvastatin might inhibit protein prenylation and MAPK activation.

CONCLUSION:

The data from this study support the belief that fluvastatin has multiple profound effects in monocyte activity, which might contribute to thrombosis prevention in APS patients.

PMID:
21173016
DOI:
10.1136/ard.2010.135525
[Indexed for MEDLINE]
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