title: Identification of candidate genes linking systemic inflammation to atherosclerosis; results of a human in vivo LPS infusion study.
abstract: BACKGROUND
  It is widely accepted that atherosclerosis and inflammation are intimately linked. Monocytes play a key role in both of these processes and we hypothesized that activation of inflammatory pathways in monocytes would lead to, among others, proatherogenic changes in the monocyte transcriptome. Such differentially expressed genes in circulating monocytes would be strong candidates for further investigation in disease association studies.
  
  
  METHODS
  Endotoxin, lipopolysaccharide (LPS), or saline control was infused in healthy volunteers. Monocyte RNA was isolated, processed and hybridized to Hver 2.1.1 spotted cDNA microarrays. Differential expression of key genes was confirmed by RT-PCR and results were compared to in vitro data obtained by our group to identify candidate genes.
  
  
  RESULTS
  All subjects who received LPS experienced the anticipated clinical response indicating successful stimulation. One hour after LPS infusion, 11 genes were identified as being differentially expressed; 1 down regulated and 10 up regulated. Four hours after LPS infusion, 28 genes were identified as being differentially expressed; 3 being down regulated and 25 up regulated. No genes were significantly differentially expressed following saline infusion. Comparison with results obtained in in vitro experiments lead to the identification of 6 strong candidate genes (BATF, BID, C3aR1, IL1RN, SEC61B and SLC43A3)
  
  
  CONCLUSIONS
  In vivo endotoxin exposure of healthy individuals resulted in the identification of several candidate genes through which systemic inflammation links to atherosclerosis.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands. s.sivapalaratnam@amc.uva.nl
authors.forename: Suthesh
authors.initials: S
authors.lastname: Sivapalaratnam
authors.forename: Rosienne
authors.initials: R
authors.lastname: Farrugia
authors.forename: Max
authors.initials: M
authors.lastname: Nieuwdorp
authors.forename: Cordelia F
authors.initials: CF
authors.lastname: Langford
authors.forename: Rachel T
authors.initials: RT
authors.lastname: van Beem
authors.forename: Stephanie
authors.initials: S
authors.lastname: Maiwald
authors.forename: Jaap Jan
authors.initials: JJ
authors.lastname: Zwaginga
authors.forename: Arief
authors.initials: A
authors.lastname: Gusnanto
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Watkins
authors.forename: Mieke D
authors.initials: MD
authors.lastname: Trip
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
mesh_terms: D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D055815:Young Adult
chemical_list: D008070:Lipopolysaccharides