Increased expression of cell-cell signaling genes by stimulated mononuclear leukocytes in patients with previous atherothrombotic stroke. A whole genome expression profile study.
OBJECTIVE
Inflammation plays an important role in atherosclerosis and stroke. Acute infections are recognized as trigger factors for ischemic stroke.


METHODS
In this whole genome expression profile study of 15 patients and 15 control subjects, we tested the hypothesis that patients with a history of atherothrombotic stroke show enhanced transcription of inflammatory genes in circulating leukocytes. RNA from unstimulated or lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) was analyzed with Affymetrix U133A GeneChips using a pooling design. Expression of single genes and functional groups of genes was analyzed by global statistical tests.


RESULTS
A total of 10,197 probe sets showed positive calls. After correction for multiple testing no single probe set revealed significant differences either without or with LPS stimulation. However, significant global expression differences were found upon LPS stimulation for the group of genes that are involved in cell-cell signaling.


CONCLUSIONS
LPS stimulation of PBMCs, a condition mimicking bacterial infection, induces differential expression of a group of cell-cell signaling genes in patients with previous atherothrombotic stroke. This finding can be caused by genetic differences between both groups, but acquired risk factors, medication and technical factors may also have contributed to the result.
Grond-Ginsbach
Caspar
C
Department of Neurology, University of Heidelberg, Heidelberg, Germany. Caspar.Grond-Ginsbach@med.uni-heidelberg.de
Horstmann
Solveig
S
Hummel
Manuela
M
Wiest
Tina
T
Honold
Cornelius
C
Pfleger
Karin
K
Hergenhahn
Manfred
M
Hollstein
Monika
M
Weninger
Annette
A
Knyazev
Yuri
Y
Mansmann
Ulrich
U
Wagner
Simone
S
Grau
Armin J
AJ
D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000097:blood / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D016678:Genome; D006801:Humans / Q000235:genetics; D007249:Inflammation / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D020521:Stroke / Q000097:blood / Q000235:genetics*
D008070:Lipopolysaccharides