title: Gene profiling reveals specific molecular pathways in the pathogenesis of atherosclerosis and cardiovascular disease in antiphospholipid syndrome, systemic lupus erythematosus and antiphospholipid syndrome with lupus.
abstract: OBJECTIVE
  To identify shared and differential molecular pathways involved in the pathogenesis of atherosclerosis (AT) and cardiovascular disease (CVD) in systemic lupus erythematosus (SLE), primary antiphospholipid syndrome (APS) and APS associated with SLE (APS plus SLE).
  
  
  METHODS
  129 patients (42 APS, 31 APS plus SLE and 56 SLE) and 61 healthy donors were included. Microarray expression profiling was performed in monocytes. RT-PCR of selected genes and western blot were used to validate microarray data. Clinical and inflammatory parameters were also analysed.
  
  
  RESULTS
  Compared with controls, 555, 1224 and 518 genes were differentially expressed in monocytes from SLE, APS plus SLE and APS patients, respectively. Approximately 25-30% of differentially expressed genes were related to AT and CVD. Each disease displayed a specific AT/CVD/Inflammation-related gene signature. Compared with SLE, APS showed alterations in mitochondria biogenesis and function and oxidative stress. Besides the interferon signature, found in APS plus SLE and SLE patients, various genes mediating atherosclerotic/inflammatory signalling were also differentially expressed in APS plus SLE. IgG-anticardiolipin (aCL) titres independently predicted both atherosclerotic and thrombosis in APS plus SLE. Moreover, a significant correlation of IgG-aCL titres with mRNA levels of certain inflammatory molecules in monocytes was further noticed. In vitro treatment of monocytes with IgG-aCL promoted an increase in the expression of the genes most significantly changed in APS plus SLE versus healthy donors.
  
  
  CONCLUSIONS
  Gene expression profiling allows the segregation of APS, APS plus SLE and SLE, with specific signatures explaining the pro-atherosclerotic and pro-thrombotic alterations in these highly related autoimmune diseases.
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: Nuria
authors.initials: N
authors.lastname: Barbarroja
authors.affiliation: Dipartimento di Scienze della Salute, Universitá Magna Graecia di Catanzaro, Catanzaro, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Messineo
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: Antonio
authors.initials: A
authors.lastname: Rodriguez-Ariza
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Jimenez-Gomez
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: 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: M 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: M Angeles
authors.initials: MA
authors.lastname: Aguirre
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; D017152:Antibodies, Antiphospholipid / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology*; D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology*; D016022:Case-Control Studies; D015897:Comorbidity; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*
chemical_list: D017152:Antibodies, Antiphospholipid; D015415:Biomarkers
keywords: Systemic lupus erythematosus; atherosclerosis; cardiovascular disease; gene profile