title: Gene expression in peripheral immune cells following cardioembolic stroke is sexually dimorphic.
abstract: OBJECTIVE
  Epidemiological studies suggest that sex has a role in the pathogenesis of cardioembolic stroke. Since stroke is a vascular disease, identifying sexually dimorphic gene expression changes in blood leukocytes can inform on sex-specific risk factors, response and outcome biology. We aimed to examine the sexually dimorphic immune response following cardioembolic stroke by studying the differential gene expression in peripheral white blood cells.
  
  
  RESULTS
  Blood samples from patients with cardioembolic stroke were obtained at ≤3 hours (prior to treatment), 5 hours and 24 hours (after treatment) after stroke onset (n = 23; 69 samples) and compared with vascular risk factor controls without symptomatic vascular diseases (n = 23, 23 samples) (ANCOVA, false discovery rate p≤0.05, |fold change| ≥1.2). mRNA levels were measured on whole-genome Affymetrix microarrays. There were more up-regulated than down-regulated genes in both sexes, and females had more differentially expressed genes than males following cardioembolic stroke. Female gene expression was associated with cell death and survival, cell-cell signaling and inflammation. Male gene expression was associated with cellular assembly, organization and compromise. Immune response pathways were over represented at ≤3, 5 and 24 h after stroke in female subjects but only at 24 h in males. Neutrophil-specific genes were differentially expressed at 3, 5 and 24 h in females but only at 5 h and 24 h in males.
  
  
  CONCLUSIONS
  There are sexually dimorphic immune cell expression profiles following cardioembolic stroke. Future studies are needed to confirm the findings using qRT-PCR in an independent cohort, to determine how they relate to risk and outcome, and to compare to other causes of ischemic stroke.
authors.affiliation: Department of Neurology and MIND Institute, University of California Davis, Sacramento, California, United States of America.
authors.forename: Boryana
authors.initials: B
authors.lastname: Stamova
authors.affiliation: Department of Neurology and MIND Institute, University of California Davis, Sacramento, California, United States of America.
authors.forename: Glen C
authors.initials: GC
authors.lastname: Jickling
authors.affiliation: Department of Neurology and MIND Institute, University of California Davis, Sacramento, California, United States of America.
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Ander
authors.affiliation: Department of Neurology and MIND Institute, University of California Davis, Sacramento, California, United States of America.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhan
authors.affiliation: Department of Neurology and MIND Institute, University of California Davis, Sacramento, California, United States of America.
authors.forename: DaZhi
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Neurology and MIND Institute, University of California Davis, Sacramento, California, United States of America.
authors.forename: Renee
authors.initials: R
authors.lastname: Turner
authors.affiliation: Department of Neurology and MIND Institute, University of California Davis, Sacramento, California, United States of America.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Ho
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Khoury
authors.affiliation: Department of Neurology, Wake Forest University Medical Center, Winston-Salem, North Carolina, United States of America.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Bushnell
authors.affiliation: Department of Emergency Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Arthur
authors.initials: A
authors.lastname: Pancioli
authors.affiliation: Division of Emergency Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Jauch
authors.affiliation: University of Cincinnati Neuroscience Institute, Department of Neurology, Cincinnati, Ohio, United States of America.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Broderick
authors.affiliation: Department of Neurology and MIND Institute, University of California Davis, Sacramento, California, United States of America.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Sharp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004900:Erythroblasts / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006331:Heart Diseases / Q000150:complications; D006801:Humans; D007249:Inflammation / Q000235:genetics; D020766:Intracranial Embolism / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D012727:Sex Characteristics; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors