Global effects of fluvastatin on the prothrombotic status of patients with antiphospholipid syndrome. Issue 4 (20th December 2010)

• Record Type: Journal Article
• Authors: López-Pedrera, Chary; Ruiz-Limón, Patricia; Aguirre, Maria Ángeles; Barbarroja, Nuria; Pérez-Sánchez, Carlos; Buendía, Paula; Rodriguez-García, Ines-Carmen; Rodriguez-Ariza, Antonio; Collantes-Estevez, Eduardo; Velasco, Francisco; Khasmahta, Munther; Cuadrado, Maria José
• Is Part Of: Annals of the rheumatic diseases. Volume 70:Issue 4(2011)
• Page Start: 675
• Page End: 682
• Publication Date: 2010-12-20
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.2010.135525
• Languages: English
• ISSNs: 0003-4967

Abstract

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.