title: Monocyte gene-expression profile in men with familial combined hyperlipidemia and its modification by atorvastatin treatment.
abstract: OBJECTIVE
  The genetic origin of familial combined hyperlipidemia (FCH) is not well understood. We used microarray profiling of peripheral blood monocytes to search novel genes and pathways involved in FCH.
  
  
  METHODS
  Fasting plasma for determination of lipid profiles, inflammatory molecules and adipokines was obtained and peripheral blood monocytes were isolated from male FCH patients basally and after 4 weeks of atorvastatin treatment. Sex-, age- and adiposity-matched controls were also studied. Gene-expression profiles were analyzed using Affymetrix Human Genome U133A 2.0 GeneChip arrays.
  
  
  RESULTS
  Analysis of gene expression by cDNA microarrays showed that 82 genes were differentially expressed in FCH monocytes compared with controls. Atorvastatin treatment modified the expression of 86 genes. Pathway analysis revealed the over-representation of the complement and coagulation cascades, the hematopoietic cell lineage and the arachidonic acid metabolism pathways. Changes in the expression of some genes, confirmed by real-time RT-PCR, (CD36, leucine-rich repeats and immunoglobulin-like domains-1, tissue factor pathway inhibitor 2, myeloid cell nuclear differentiation antigen, tumor necrosis factor receptor superfamily, member 25, CD96 and lipoprotein lipase), may be related to a proinflammatory environment in FCH monocytes, which is partially reversed by atorvastatin. Higher plasma levels of triglycerides and free fatty acids and lower levels of adiponectin in FCH patients could also trigger changes in gene expression that atorvastatin cannot modify.
  
  
  CONCLUSIONS
  Our results show clear differences in gene expression in FCH monocytes compared with those of matched healthy controls, some of which are influenced by atorvastatin treatment.
authors.affiliation: Pharmacology Department, Faculty of Pharmacy and Biomedicine Institute (IBUB), University of Barcelona and Ciber Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Instituto de Salud Carlos III, Diagonal 643. E-08028, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Llaverias
authors.forename: Jordi
authors.initials: J
authors.lastname: Pou
authors.forename: Emilio
authors.initials: E
authors.lastname: Ros
authors.forename: Daniel
authors.initials: D
authors.lastname: Zambón
authors.forename: Montserrat
authors.initials: M
authors.lastname: Cofán
authors.forename: Alex
authors.initials: A
authors.lastname: Sánchez
authors.forename: Manuel
authors.initials: M
authors.lastname: Vázquez-Carrera
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Sánchez
authors.forename: Juan C
authors.initials: JC
authors.lastname: Laguna
authors.forename: Marta
authors.initials: M
authors.lastname: Alegret
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D020869:Gene Expression Profiling / Q000379:methods*; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D006538:Heptanoic Acids; D018836:Inflammation Mediators; D011758:Pyrroles; D000069059:Atorvastatin