title: Gene expression in human peripheral blood mononuclear cells upon acute ischemic stroke.
abstract: OBJECTIVE
  Ischemic stroke provokes a systemic inflammatory response. The purpose of this study was to characterize this response on the gene expression level in circulating mononuclear leukocytes from acute ischemic stroke (AIS) patients.
  
  
  METHODS
  RNA from peripheral blood mononuclear cells (PBMCs) of AIS patients (24 + 2 hours after onset of symptoms) was analyzed with Affymetrix U133A GeneChips using a pooled design. We compared the gene expression signature from AIS patients (n = 20), stroke survivors (n = 15), patients with acute traumatic brain injury (ATBI, n = 15) and healthy control subjects without vascular risk factors (n = 15).
  
  
  RESULTS
  Expression levels of 9682 probe sets with present calls on each GeneChip were compared. Between AIS patients and stroke survivors or between AIS patients and ATBI patients there were no significant differences in expression values of single genes after correction for multiple testing. However, comparison of the PBMC expression profiles from AIS patients and healthy subjects revealed significantly different expression (p = 0.012) of a single probe set, specific for phosphodiesterase 4 D (PDE4D). In order to detect modest expression differences in multiple genes with a presumed cumulative effect we studied the gene expression of functional groups of genes by global statistical tests. Analysis of 11 gene groups revealed differential expression between AIS patients and healthy subjects for genes involved in the inflammatory response (GeneOntology GO:0006954). Genes encoding the N-formyl peptide receptor-like 1 (FPRL1), interleukin-1 receptor antagonist (IL1RN) and complement component 3a receptor 1 (C3AR1) contributed most to the observed difference.
  
  
  CONCLUSIONS
  This transcriptome analysis did not identify significant changes between circulating mononuclear cells from AIS patients 24 hours after stroke and closely matched stroke survivors. However, comparing AIS patients with healthy control subjects revealed measurable differences in PDE4D and in inflammatory response genes when considered as a set.
authors.affiliation: Dept. of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Caspar_Grond-Ginsbach@med.uni-heidelberg.de
authors.forename: C
authors.initials: C
authors.lastname: Grond-Ginsbach
authors.forename: M
authors.initials: M
authors.lastname: Hummel
authors.forename: T
authors.initials: T
authors.lastname: Wiest
authors.forename: S
authors.initials: S
authors.lastname: Horstmann
authors.forename: K
authors.initials: K
authors.lastname: Pfleger
authors.forename: M
authors.initials: M
authors.lastname: Hergenhahn
authors.forename: M
authors.initials: M
authors.lastname: Hollstein
authors.forename: U
authors.initials: U
authors.lastname: Mansmann
authors.forename: A J
authors.initials: AJ
authors.lastname: Grau
authors.forename: S
authors.initials: S
authors.lastname: Wagner
mesh_terms: D000208:Acute Disease; D000368:Aged; D002545:Brain Ischemia / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011951:Receptors, Complement / Q000235:genetics; D044042:Receptors, Formyl Peptide / Q000235:genetics; D044067:Receptors, Lipoxin / Q000235:genetics; D020521:Stroke / Q000097:blood / Q000235:genetics* / Q000503:physiopathology
chemical_list: C105101:FPR2 protein, human; D005819:Genetic Markers; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D011951:Receptors, Complement; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C085567:complement C3a receptor; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4