title: Atherosclerosis and cardiovascular disease in systemic lupus erythematosus: effects of in vivo statin treatment.
abstract: OBJECTIVE
  Statins may have beneficial vascular effects in systemic lupus erythematosus (SLE) beyond their cholesterol-lowering action, although the mechanisms involved are not completely understood. We investigated potential mechanisms involved in the efficacy of fluvastatin in preventing atherothrombosis in SLE.
  
  
  METHODS
  Eighty-five patients with SLE and 62 healthy donors were included in the study. Selected patients (n=27) received 20 mg/day fluvastatin for 1 month. Blood samples were obtained before the start and at the end of treatment. Monocytes from five patients were treated in vitro with fluvastatin.
  
  
  RESULTS
  Increased prothrombotic and inflammatory variables were found in patients with SLE. SLE monocytes displayed altered mitochondrial membrane potential and increased oxidative stress. Correlation and association analyses demonstrated a complex interplay among autoimmunity, oxidative stress, inflammation and increased risk of atherothrombosis in SLE. Fluvastatin treatment of patients for 1 month reduced the SLE Disease Activity Index and lipid levels, oxidative status and vascular inflammation. Array studies on monocytes demonstrated differential expression in 799 genes after fluvastatin treatment. Novel target genes and pathways modulated by fluvastatin were uncovered, including gene networks involved in cholesterol and lipid metabolism, inflammation, oxidative stress and mitochondrial activity. Electron microscopy analysis showed increased density volume of mitochondria in monocytes from fluvastatin-treated patients, who also displayed higher expression of genes involved in mitochondrial biogenesis. In vitro treatment of SLE monocytes confirmed the results obtained in the in vivo study.
  
  
  CONCLUSIONS
  Our overall data suggest that fluvastatin improves the impairment of a redox-sensitive pathway involved in processes that collectively orchestrate the pathophysiology of atherothrombosis in SLE.
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ruiz-Limon
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Barbarroja
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Perez-Sanchez
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain.
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Aguirre
authors.affiliation: Graham Hughes Lupus Research Laboratory, The Rayne Institute, King's College London, London, UK.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Bertolaccini
authors.affiliation: Graham Hughes Lupus Research Laboratory, The Rayne Institute, King's College London, London, UK.
authors.forename: Munther A
authors.initials: MA
authors.lastname: Khamashta
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodriguez-Ariza
authors.affiliation: Lipid and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Almadén
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Segui
authors.affiliation: University of Cordoba, Campus de Excelencia Internacional Agroalimentario, Cordoba, Spain.
authors.forename: Husam
authors.initials: H
authors.lastname: Khraiwesh
authors.affiliation: University of Cordoba, Campus de Excelencia Internacional Agroalimentario, Cordoba, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Gonzalez-Reyes
authors.affiliation: University of Cordoba, Campus de Excelencia Internacional Agroalimentario, Cordoba, Spain.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Villalba
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Collantes-Estevez
authors.affiliation: Graham Hughes Lupus Research Laboratory, The Rayne Institute, King's College London, London, UK.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Cuadrado
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain.
authors.forename: Chary
authors.initials: C
authors.lastname: Lopez-Pedrera
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000503:physiopathology / Q000517:prevention & control*; D002318:Cardiovascular Diseases / Q000503:physiopathology / Q000517:prevention & control*; D016022:Case-Control Studies; D002478:Cells, Cultured; D015897:Comorbidity; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin
keywords: Atherosclerosis; Cardiovascular Disease; Systemic Lupus Erythematosus; Treatment