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Atherosclerosis and cardiovascular disease in systemic lupus erythematosus: effects of in vivo statin treatment
  1. Patricia Ruiz-Limon1,
  2. Nuria Barbarroja1,
  3. Carlos Perez-Sanchez1,
  4. Maria Angeles Aguirre1,
  5. Maria Laura Bertolaccini2,
  6. Munther A Khamashta2,
  7. Antonio Rodriguez-Ariza1,
  8. Yolanda Almadén3,
  9. Pedro Segui1,
  10. Husam Khraiwesh4,
  11. Jose Antonio Gonzalez-Reyes4,
  12. Jose Manuel Villalba4,
  13. Eduardo Collantes-Estevez1,
  14. Maria Jose Cuadrado2,
  15. Chary Lopez-Pedrera1
  1. 1Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain
  2. 2Graham Hughes Lupus Research Laboratory, The Rayne Institute, King's College London, London, UK
  3. 3Lipid and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain
  4. 4University of Cordoba, Campus de Excelencia Internacional Agroalimentario, Cordoba, Spain
  1. Correspondence to Dr Chary López-Pedrera, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Avda Menéndez Pidal s/n, Córdoba E-14004, Spain; rosario.lopez.exts{at}


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.

  • Cardiovascular Disease
  • Systemic Lupus Erythematosus
  • Treatment
  • Atherosclerosis

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