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

Boryana Stamova, Glen C. Jickling, Bradley Ander, Xinhua Zhan, Da Liu, Renee Turner, Carolyn Ho, Jane C. Khoury, Cheryl Bushnell, Arthur Pancioli, Edward C. Jauch, Joseph P. Broderick, Frank R Sharp

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Aims: 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. Methods and 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.

Original languageEnglish (US)
Article numbere102550
JournalPLoS One
Volume9
Issue number7
DOIs
StatePublished - Jul 18 2014

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stroke
Gene expression
Genes
Stroke
Gene Expression
gene expression
Blood
cells
Cell signaling
vascular diseases
Cell death
Microarrays
Vascular Diseases
gender
leukocytes
Cells
Leukocytes
risk factors
immune response
Messenger RNA

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Gene expression in peripheral immune cells following cardioembolic stroke is sexually dimorphic. / Stamova, Boryana; Jickling, Glen C.; Ander, Bradley; Zhan, Xinhua; Liu, Da; Turner, Renee; Ho, Carolyn; Khoury, Jane C.; Bushnell, Cheryl; Pancioli, Arthur; Jauch, Edward C.; Broderick, Joseph P.; Sharp, Frank R.

In: PLoS One, Vol. 9, No. 7, e102550, 18.07.2014.

Research output: Contribution to journalArticle

Stamova, B, Jickling, GC, Ander, B, Zhan, X, Liu, D, Turner, R, Ho, C, Khoury, JC, Bushnell, C, Pancioli, A, Jauch, EC, Broderick, JP & Sharp, FR 2014, 'Gene expression in peripheral immune cells following cardioembolic stroke is sexually dimorphic', PLoS One, vol. 9, no. 7, e102550. https://doi.org/10.1371/journal.pone.0102550
Stamova, Boryana ; Jickling, Glen C. ; Ander, Bradley ; Zhan, Xinhua ; Liu, Da ; Turner, Renee ; Ho, Carolyn ; Khoury, Jane C. ; Bushnell, Cheryl ; Pancioli, Arthur ; Jauch, Edward C. ; Broderick, Joseph P. ; Sharp, Frank R. / Gene expression in peripheral immune cells following cardioembolic stroke is sexually dimorphic. In: PLoS One. 2014 ; Vol. 9, No. 7.
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AU - Khoury, Jane C.

AU - Bushnell, Cheryl

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AB - Aims: 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. Methods and 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.

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