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PLoS One. 2014 Jul 18;9(7):e102550. doi: 10.1371/journal.pone.0102550. eCollection 2014.

Gene expression in peripheral immune cells following cardioembolic stroke is sexually dimorphic.

Author information

  • 1Department of Neurology and MIND Institute, University of California Davis, Sacramento, California, United States of America.
  • 2Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America.
  • 3Department of Neurology, Wake Forest University Medical Center, Winston-Salem, North Carolina, United States of America.
  • 4Department of Emergency Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
  • 5Division of Emergency Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
  • 6University of Cincinnati Neuroscience Institute, Department of Neurology, Cincinnati, Ohio, United States of America.



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.


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.


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.

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