title: Global effects of fluvastatin on the prothrombotic status of patients with antiphospholipid syndrome.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: IMIBIC, Hospital Reina Sofía, Avenida Menéndez Pidal s/n, E-14004 Córdoba, Spain. rosario.lopez.exts@juntadeandalucia.es
authors.forename: Chary
authors.initials: C
authors.lastname: López-Pedrera
authors.forename: Patricia
authors.initials: P
authors.lastname: Ruiz-Limón
authors.forename: Maria Ángeles
authors.initials: MÁ
authors.lastname: Aguirre
authors.forename: Nuria
authors.initials: N
authors.lastname: Barbarroja
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez-Sánchez
authors.forename: Paula
authors.initials: P
authors.lastname: Buendía
authors.forename: Ines-Carmen
authors.initials: IC
authors.lastname: Rodriguez-García
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodriguez-Ariza
authors.forename: Eduardo
authors.initials: E
authors.lastname: Collantes-Estevez
authors.forename: Francisco
authors.initials: F
authors.lastname: Velasco
authors.forename: Munther
authors.initials: M
authors.lastname: Khasmahta
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Cuadrado
mesh_terms: D000328:Adult; D016736:Antiphospholipid Syndrome / Q000097:blood* / Q000150:complications; D016022:Case-Control Studies; D002478:Cells, Cultured; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D040901:Proteomics / Q000379:methods; D044462:Receptors, Proteinase-Activated / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000097:blood* / Q000209:etiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D016328:NF-kappa B; D044462:Receptors, Proteinase-Activated; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077340:Fluvastatin; D013925:Thromboplastin; D048051:p38 Mitogen-Activated Protein Kinases