Gene expression in peripheral blood differs after cardioembolic compared with large-vessel atherosclerotic stroke: biomarkers for the etiology of ischemic stroke.
There are no biomarkers that differentiate cardioembolic from large-vessel atherosclerotic stroke, although the treatments differ for each and approximately 30% of strokes and transient ischemic attacks have undetermined etiologies using current clinical criteria. We aimed to define gene expression profiles in blood that differentiate cardioembolic from large-vessel atherosclerotic stroke. Peripheral blood samples were obtained from healthy controls and acute ischemic stroke patients (<3, 5, and 24 h). RNA was purified, labeled, and applied to Affymetrix Human U133 Plus 2.0 Arrays. Expression profiles in the blood of cardioembolic stroke patients are distinctive from those of large-vessel atherosclerotic stroke patients. Seventy-seven genes differ at least 1.5-fold between them, and a minimum number of 23 genes differentiate the two types of stroke with at least 95.2% specificity and 95.2% sensitivity for each. Genes regulated in large-vessel atherosclerotic stroke are expressed in platelets and monocytes and modulate hemostasis. Genes regulated in cardioembolic stroke are expressed in neutrophils and modulate immune responses to infectious stimuli. This new method can be used to predict whether a stroke of unknown etiology was because of cardioembolism or large-vessel atherosclerosis that would lead to different therapy. These results have wide ranging implications for similar disorders.
Xu
Huichun
H
Department of Neurology and MIND Institute, University of California at Davis, Sacramento, California 95817, USA. huixu@ucdavis.edu
Tang
Yang
Y
Liu
Da-Zhi
DZ
Ran
Ruiqiong
R
Ander
Bradley P
BP
Apperson
Michelle
M
Liu
Xin She
XS
Khoury
Jane C
JC
Gregg
Jeffrey P
JP
Pancioli
Arthur
A
Jauch
Edward C
EC
Wagner
Kenneth R
KR
Verro
Piero
P
Broderick
Joseph P
JP
Sharp
Frank R
FR
D050197:Atherosclerosis / Q000150:complications*; D015415:Biomarkers / Q000097:blood; D001773:Blood Cells; D001792:Blood Platelets; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D004617:Embolism / Q000150:complications*; D020869:Gene Expression Profiling / Q000379:methods / Q000592:standards; D006801:Humans; D009000:Monocytes; D009504:Neutrophils; D012680:Sensitivity and Specificity; D020521:Stroke / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics*
D015415:Biomarkers