Top five over-represented canonical pathways in cardioembolic stroke; Benjamini-Hochberg P-value <0.05.

<p>Top five over-represented canonical pathways in cardioembolic stroke; Benjamini-Hochberg P-value <0.05.</p

Gene Expression in Peripheral Immune Cells following Cardioembolic Stroke Is Sexually Dimorphic

<div><p>Aims</p><p>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.</p><p>Methods and Results</p><p>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.</p><p>Conclusions</p><p>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.</p></div

Over-represented categories in the female-specific and/or male-specific genes regulated at ≤3 hours following cardioembolic stroke.

<p>Categories above the orange line are significant at Benjamini-Hochberg corrected P-value <0.05.</p

Genes differentially expressed in female and male following cardioembolic stroke.

<p>* -genes with female-specific expression; ** -genes with male-specific expression.</p

Cell-type specific gene expression in female and male following cardioembolic stroke.

<p>Y-axis - % of genes from our gene list, which overlap with a cell-type specific gene list from Watkins et al, 2007. * p<0.05; **P<0.005; # hypergeometric probability of overlap between our gene list and the cell-type specific gene list from Watkins et al, 2007<0.05; ∧ Watkins et al used positive selection, therefore granulocyte population consisted of three cell types (neutrophils, eosinophils, and basophils), all of which expressed CD66b and would have therefore been co-purified. However, the neutrophils are the largest percent.</p

Subject characteristics.

<p>Subject characteristics.</p