TY - JOUR
T1 - Gene Expression Profiling of Blood in Brain Arteriovenous Malformation Patients
AU - Weinsheimer, Shantel M.
AU - Xu, Huichun
AU - Achrol, Achal S.
AU - Stamova, Boryana
AU - McCulloch, Charles E.
AU - Pawlikowska, Ludmila
AU - Tian, Yingfang
AU - Ko, Nerissa U.
AU - Lawton, Michael T.
AU - Steinberg, Gary K.
AU - Chang, Steven D.
AU - Jickling, Glen
AU - Ander, Bradley
AU - Kim, Helen
AU - Sharp, Frank R
AU - Young, William L.
PY - 2011/12
Y1 - 2011/12
N2 - Brain arteriovenous malformations (BAVMs) are an important cause of intracranial hemorrhage (ICH) in young adults. Gene expression profiling of blood has led to the identification of stroke biomarkers and may help identify BAVM biomarkers and illuminate BAVM pathogenesis. It is unknown whether blood gene expression profiles differ between (1) BAVM patients and healthy controls or (2) unruptured and ruptured BAVM patients at presentation. We characterized blood transcriptional profiles in 60 subjects (20 unruptured BAVM, 20 ruptured BAVM, and 20 healthy controls) using Affymetrix whole genome expression arrays. Expression differences between groups were tested by ANOVA, adjusting for potential confounders. Genes with absolute fold change ≥1. 2 (false discovery rate corrected p ≤ 0. 1) were selected as differentially expressed and evaluated for over-representation in KEGG biological pathways (p ≤ 0. 05). Twenty-nine genes were differentially expressed between unruptured BAVM patients and controls, including 13 which may be predictive of BAVM. Patients with ruptured BAVM compared to unruptured BAVM differed in expression of 1,490 genes, with over-representation of genes in 8 pathways including MAPK, VEGF, Wnt signaling, and several inflammatory pathways. These results suggest clues to the pathogenesis of BAVM and/or BAVM rupture and point to potential biomarkers or new treatment targets.
AB - Brain arteriovenous malformations (BAVMs) are an important cause of intracranial hemorrhage (ICH) in young adults. Gene expression profiling of blood has led to the identification of stroke biomarkers and may help identify BAVM biomarkers and illuminate BAVM pathogenesis. It is unknown whether blood gene expression profiles differ between (1) BAVM patients and healthy controls or (2) unruptured and ruptured BAVM patients at presentation. We characterized blood transcriptional profiles in 60 subjects (20 unruptured BAVM, 20 ruptured BAVM, and 20 healthy controls) using Affymetrix whole genome expression arrays. Expression differences between groups were tested by ANOVA, adjusting for potential confounders. Genes with absolute fold change ≥1. 2 (false discovery rate corrected p ≤ 0. 1) were selected as differentially expressed and evaluated for over-representation in KEGG biological pathways (p ≤ 0. 05). Twenty-nine genes were differentially expressed between unruptured BAVM patients and controls, including 13 which may be predictive of BAVM. Patients with ruptured BAVM compared to unruptured BAVM differed in expression of 1,490 genes, with over-representation of genes in 8 pathways including MAPK, VEGF, Wnt signaling, and several inflammatory pathways. These results suggest clues to the pathogenesis of BAVM and/or BAVM rupture and point to potential biomarkers or new treatment targets.
KW - Arteriovenous malformation
KW - Blood
KW - Gene expression
KW - Intracranial hemorrhage
KW - Microarray analysis
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U2 - 10.1007/s12975-011-0103-3
DO - 10.1007/s12975-011-0103-3
M3 - Article
C2 - 22184505
AN - SCOPUS:83355166837
VL - 2
SP - 575
EP - 587
JO - Translational Stroke Research
JF - Translational Stroke Research
SN - 1868-4483
IS - 4
ER -